Cleaning up the invisible trail of biological poison left by the anthrax letters mailed last year will cost hundreds of millions of dollars by the time the decontamination effort is complete in 2004 or later, government officials say.

The cleanup reached a new peak this week, with the long-delayed fumigation of the huge Brentwood mail-sorting facility in northeast Washington and the start of what is expected to be an 18-month rehabilitation of the State Department's mail facility in Sterling, Va.

The human tragedy of the attacks - five dead, including two Brentwood workers, and at least 17 cases of illness - has been well-documented. But the economic impact of a few teaspoons of fine-grained powder spilled from seven letters has turned out to be far greater than experts anticipated.

"The economic costs are huge," said Dorothy A. Canter, chief scientist for bioterrorism issues at the Environmental Protection Agency, who is tracking the decontamination work. "It's in the hundreds of millions of dollars for the cleanup alone."

To reduce the chance that a new biological assault could again devastate the nation's postal system, undoing all the decontamination work, the Postal Service is testing germ detectors at Baltimore's main postal facility on Fayette Street.

Based on preliminary results with the biological detection system, designed by Northrop Grumman Corp., the equipment will be installed in 14 more postal facilities for further testing, said Postal Service spokesman Bob Novak. The detectors are designed to identify about a dozen potential biological agents, including anthrax.

In the weeks after the anthrax attacks, hundreds of federal offices in all three branches of the federal government were evacuated. The Bush administration more than quadrupled spending on preparedness for bioterrorism, wrenching the public health system from routine prenatal care and AIDS prevention to cope with such exotic threats as smallpox.

Meanwhile, anthrax cleanup costs have skyrocketed. No precise estimate is possible, officials say, because most of the work is still ahead.

But the Postal Service says decontaminating Brentwood and another sorting center in Hamilton Township, N.J., will cost "in excess of $100 million." The bill for decontaminating the Hart Senate Office Building and other Capitol Hill offices cost the EPA and its contractors about $42 million, according to figures provided by the EPA to Iowa Republican Sen. Charles E. Grassley, who has asked the General Accounting Office for a review. Many millions more have been spent testing and cleaning other government and postal buildings.

The costs were driven up, officials say, by months of trial-and-error experiments to find reliable, safe ways of killing the hardy anthrax spores.

In heavily contaminated buildings, costly furnishings, computers, carpets and even drywall have had to be ripped out. Environmental regulations require elaborate paperwork before toxic chlorine dioxide gas is used or contaminated materials are incinerated.

"We've never had to do anything like this in history," said Barbara Johnson, president of the American Biological Safety Assoc., an organization of about 1,000 professionals in the field. "The government is erring very, very much on the side of safety. It's a very conservative approach, but I don't think there's any other choice."

Officials say they have moved cautiously to be certain buildings are safe before traumatized workers move back in. Postal employees in particular feel they were recklessly endangered last year when officials failed to close the Brentwood facility or to give workers antibiotics when anthrax was discovered.

"Some people are ready to go back," said Dena Briscoe, a 22-year postal employee and president of Brentwood Exposed, an advocacy group representing workers of the closed facility. "But a lot of people still have fears. Some people just wish the building could be abandoned. Knowing that the person who mailed the anthrax has never been caught really heightens our fears."

The legal watchdog group Judicial Watch submitted documents this month to prosecutors seeking a criminal investigation of the delay in closing Brentwood. The group also filed a complaint with the Equal Employment Opportunity Commission, asserting that Brentwood workers, most of whom are black, were not given the same treatment as the predominantly white congressional employees.

Last weekend, chlorine dioxide gas was pumped into the 700,000-square-foot Brentwood mail center, recently renamed for the two postal workers who died after contracting inhalation anthrax there, Joseph Curseen Jr. and Thomas Morris Jr.

This week, workers in biohazard suits re-entered the building and began to collect more than 8,000 strips embedded with spores of a nontoxic bacteria very similar to anthrax.

By mid-January, the results should determine whether all the spores were killed. If all goes well, the Postal Service hopes to reopen the facility in April.

The cleanup strategy was pioneered this year by the EPA at the Hart building, where an anthrax-laced letter addressed to Senate Democratic leader Tom Daschle was opened.

"Essentially you have an engineering project here that has never been done before," said Postal Service spokesman Greg Frey of the Brentwood cleanup. "It's on a much, much larger scale than Hart," he added - about 90,000 cubic feet for the Daschle suites fumigated in the Hart building, compared with 14 million cubic feet at Brentwood.

For the fumigation, the building had to be completely sealed and humidity increased to 75 percent, making the spores vulnerable, postal officials say.

At least one other major building, the former offices of American Media Inc., the tabloid newspaper company in Boca Raton, Fla., where the first victim worked, remains closed and abandoned, with no immediate plans for decontamination.

As the Brentwood decontamination went on, about 100 FBI agents have conducted a search of ponds and woods in a watershed area near Frederick, apparently looking for equipment used to make the anthrax. Former Army bioterrorism expert Steven J. Hatfill, who has been the focus of anthrax investigators for months, lived in Frederick until last summer. He has denied any connection to the attacks.

"They've been taking things out of two fire ponds and labeling everything and taking it away," said Nancy Gregg Poss, a spokeswoman for the city of Frederick. "If they found what they're looking for, we still don't know."