Five recipients of successful living related donor kidney transplants stopped azathioprine and prednisone against medical advice. Two recipients who were nonidentical by human leukocyte (HL-A) serotyping and mixed leukocyte culture (MLC) became uremic again after cessation of immunosuppression for periods of 2 and 6 mo. Both patients died while refusing to reinstitute inunosuppression and their kidneys showed severe rejection histologically. Three recipients of MLC and HL-A identical kidneys were off azathioprine and prednisone for periods of 7, 12 and 30 mo., respectivly. None developed changes in renal function. Two patients currently are back on immunosuppression. The 3rd recipient remains stable although off immunosuppression for 36 mo.; her cessation of immunosuppression was elicited by a mailed questionnaire sent to all recipients following detection of the first 4. In addition to these 5 patients, 3 recipients of cadaver kidneys lost graft function after lapses in immunosuppression. This represents a 4% incidence of major lapses in immunosuppression (excluding known cessation during sepsis). The clinical outcome depended on degree of histocompatibility as best measured by MLC.