Decreasing federal and state support threaten long-term sustainability of research in publicly supported academic health centers. In weathering these financial threats, research at the University of California, San Francisco (UCSF) has undergone substantial changes. Lacking a general endowment, UCSF relies mainly on indirect cost recovery from research grants for institutional support of research programs, and on private gifts and debt for constructing new laboratories. Institutional salary support goes preferentially to senior faculty, while the young increasingly depend on grants. Private and government support for research grows apace in clinical departments, but slowly declines in basic science departments. Research is judged more on its quantity (numbers of investigators and federal and private dollars) than on its goals, achievements, or scientific quality. We propose measures to help UCSF alleviate these problems. Similar issues may afflict research at other large public academic health centers, which have not been carefully studied.