Agre, 59, will be director of the Malaria Research Institute at the Hopkins Bloomberg School of Public Health.
Agre said he was returning largely for the malaria challenge. "I'm really excited about this," he said yesterday. "Taking the malaria job is something I've been very eager to do."
The return is also a vindication of sorts for Hopkins, whose administration drew criticism for not doing enough to keep Agre when he left for Duke. Dr. Michael Klag, dean of the School of Public Health, said Agre will boost the institute's profile.
"He's a very innovative guy. This will create lots of opportunities for advances," said Klag, who has known Agre for more than two decades.
Malaria, which is caused by a parasite spread by the female anopheles mosquito, annually infects 650 million people and kills up to 3 million, mostly in the poorest parts of the planet.
It has received increased attention in recent years. Many international organizations, including the United Nations and the Bill and Melinda Gates Foundation, have begun programs to fight the disease, which is widespread in sub-Saharan Africa and parts of South Asia and Latin America.
The Hopkins institute is one of the world's leading malaria research organizations. Launched with $100 million from an anonymous donor, it has 19 full-time researchers, whose projects range from developing tests to identify malaria in humans to creating new anti-malaria drugs.
Agre, who is not a malaria expert, began doing research on the disease three years ago. Since then, he and his labs at Duke and Hopkins have published two papers on the role that proteins called aquaporins play in the malaria bug's life cycle.
It was his work with aquaporins that won Agre the Nobel, and he suspects that the molecules could offer innovative ways to fight malaria.
Agre said he has long been fascinated by malaria, largely because it is so deadly and so widespread.
"If there is something we can do for malaria, I'd really like to get involved in it," he said.
He will split his time between running his own malaria research lab, overseeing the Malaria Institute, and serving as a public advocate for malaria research at Hopkins and elsewhere.
Klag said Agre will not be a "nuts-and-bolts administrator," but more of an "inspirational guy," serving as a mentor for younger scientists and articulating a larger vision for the institute.
Agre has increasingly played that kind of public role since he won the Nobel in 2003. A year ago, he appeared on The Colbert Report, a Comedy Central political satire show, to talk about the importance of science education.
After winning the Nobel Prize, Agre was showered with attention and job offers. Eventually, the demands of being a Nobel winner - almost constant travel and speaking engagements - made doing research difficult. Agre began looking for new challenges.
At a scientific conference in 2003, Agre met Dr. Victor Dzau, chancellor of health affairs and chief executive officer of the Duke University Health System. Dzau persuaded Agre to join Duke as vice chancellor of science and technology.
There, he continued to do some scientific research but focused on policy and advocacy. He traveled the world lecturing on a range of topics, including human rights, the importance of science education and his research. He also worked to come up with strategies to help Duke improve its science and technology research and education.
But he never severed his ties to Baltimore, which date to 1970 and his days as a Johns Hopkins medical student. After a brief fellowship in Cleveland and another in North Carolina, he returned in 1981, and stayed until 2005.
He and his wife, Mary, a preschool teacher, never sold their house in Stoneleigh. She and their youngest daughter continue to live there, and Peter Agre often flew up from North Carolina on weekends. At Duke, he lived in an apartment and rode his bike to work.
Yesterday, Dzau wished Agre well and said the researcher would continue to play a role, albeit a reduced one, at Duke.
"This is a great opportunity for Peter. But we don't believe we're losing him. Peter will remain connected to us," Dzau said. He said that Agre will continue to have a small lab at Duke.
Agre is most famous for his work on aquaporins, proteins that help water move in and out of cells. He and Hopkins colleague Bill Guggino discovered aquaporins in 1992.
Before that, no one had understood exactly how cells transport water. The researchers subsequently identified aquaporins in cells in human muscles, lungs and kidneys, and in the brain. Other scientists have found them in a wide range of plants and animals.
Over the past year, Agre said, he has considered other opportunities. A "lifelong Democrat," Agre has regularly criticized the Bush administration, saying it tried to muzzle scientists whose research undercuts administration policy.
He said he thought seriously about running for the Senate in Minnesota, where he was born and raised but decided against it after a poll found that he was unlikely to win the Democratic caucus endorsement.
He is also chairman of the National Academy of Sciences' human rights committee, which tries to stop persecution of scientists around the world.
Eventually, Agre said, he decided to return to Hopkins in part because living in Baltimore would allow him to be more involved in the human rights work through the National Academy in Washington.
The malaria institute, established in 2001, has been led by Dr. Diane Griffin. Yesterday Griffin praised Agre and said she is happy that he was taking over.
"I'm extremely excited to see Peter returning," said Griffin, who will remain in charge of the School of Public Health's department of molecular microbiology and Immunology. "It's always been our vision to have someone of appropriate stature take over."
As for giving up the top spot, she said that "having one fewer job sounds wonderful."