The proposed training program seeks to continue to provide multidisciplinary postgraduate research training in academic nephrology to individuals who have previously earned M.D., and/or Ph.D. degrees. Individuals accepted into this program will spend three or more years in essentially full-time laboratory research. The program will be enriched with a regularly scheduled series of lectures and seminars; participants are also encouraged to enroll in some formal postgraduate course work within Harvard University. It is our belief that the most important component of the proposed program is the intense and virtually undisturbed involvement of trainees in ongoing research projects within the applicant institution, with close and continuous supervision provided by faculty preceptors who are themselves the recipients and principal investigators of NIH supported research programs. Emphasis will be placed on integration of basic and applied nephrology. The domain of training opportunities in basic research will include the physiological, cellular and molecular biological bases of solute and fluid exchanges across renal epithelia and endothelia, physiology and pharmacology of vasoactive hormones, the immunological and non-immunological mechanisms operating in renal diseases, and the immunobiology of transplantation. These basic approaches will also be applied, wherever possible, to clinically relevant areas of investigation, including the creation of animal models of deranged functions of the kidney; extensive of immunological techniques to better define T cell recognition of cell surface antigens, and subsequent gene activation systems that lead to inflammatory immune responses, or to tolerance; the nature and control of effector mechanisms in graft rejection in animal models and in human transplant recipients. Techniques represented include protein and nucleic acid biochemistry, molecular biology, cell and tissue culture, immunocytochemistry, membrane fractionation, electrophysiology, micropuncture, and whole animal procedures.