Agre, 54, of the Johns Hopkins University School of Medicine in Baltimore, discovered in 1988 the "channels" that let water pass in and out of cells, the Royal Swedish Academy said.
MacKinnon, 47, did key studies of the structure and workings of channels that transport charged particles called ions through cell walls. He is with the Howard Hughes Medical Institute at The Rockefeller University in New York.
The research sheds light on such conditions as diabetes. Serious diseases of the nervous system, muscle and heart can result when ion channels fail to work properly. This makes ion channels important drug targets for pharmaceutical industry.
"The major impact (of the research) has been on understanding disease, perhaps not yet treating disease," said Gunnar von Heijne, a member of the Nobel Committee for chemistry.
"These are discoveries that are of fundamental importance for the understanding of life processes, not just among humans and higher organisms, but also for bacteria and plants," said Bengt Norden, chairman of the chemistry committee.
Channels are found in all living cells, and are needed for such key body activities as muscle contraction, heart function and communication between nerve cells. Kidney cells use them to remove water from urine, for example.
Because of Agre's work, researchers can follow in detail a water molecule on its way through the cell wall and understand why only water, not other small molecules or ions, can pass, the academy said.
Agre, reached at his home, said, "I'm jubilant. I'm overwhelmed, frankly. One doesn't plan to have this sort of thing happen.... Deep down in your heart a scientist will always dream about something like this."
Ion channels let cells generate and transmit electrical signals, and so are key to letting nerve cells communicate. In 1998, MacKinnon determined the first detailed structure of an ion channel, a technically challenging achievement.
Rockefeller University spokeswoman Lynn Love said Wednesday that MacKinnon was out of town and unavailable for comment.
Nobel Foundation statutes stipulate that no more than three winners can share a prize and the scientific committees often choose the maximum number, finding it hard to single out researchers. Often the awards are given for discoveries made after decades of research.
Nobel gave little guidance other than to say the chemistry prize should go to those who "shall have conferred the greatest benefit on mankind" and "shall have made the most important chemical discovery or improvement."
Last year's winners were John B. Fenn, of Virginia Commonwealth University in Richmond, Va.; Koichi Tanaka, of Shimadzu Corp. in Kyoto, Japan; and Kurt Wuethrich, a scientist with the Swiss Federal Institute of Technology in Zurich and the Scripps Research Institute in San Diego.
They were awarded for inventing techniques used to identify and analyze proteins, advances that revolutionized the hunt for new medicines and proved useful for diagnosing some cancers.
The announcements of this year's Nobel awards started last week with the literature prize going to J.M. Coetzee of South Africa.
On Monday, American Paul C. Lauterbur, and Briton Sir Peter Mansfield were selected for the 2003 Nobel Prize in physiology or medicine for discoveries leading to a technique that reveals images of the body's inner organs.
The physics prize on Tuesday went to Alexei A. Abrikosov, Anthony J. Leggett, and Vitaly L. Ginzburg, for their work concerning two phenomena called superconductivity and superfluidity.
The Nobel science awards were to culminate later Wednesday, with the economics prize, the only award not established in the will of Swedish industrialist Alfred Nobel, the inventor of dynamite.
The Nobel Peace Prize was to be announced Friday in Oslo, Norway.
The medicine, physics, chemistry, literature and peace prizes were first awarded in 1901. The Nobel Memorial Prize in Economic Sciences was established separately in 1968 by the Swedish central bank, but it is grouped with the other awards.
The prizes are presented to the winners on Dec. 10, the anniversary of Nobel's death in 1896.