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 if immunosuppression for periods of 2 and 6 months. Both patients died while refusing to reinstitute iunosuppression and their kidneys showed severe rejection histologically. Three recipients of MCL and HL-A identical kidneys were off azathioprine and prednisone for periods of 7, 12, and 30 months, respectively. None developed changes in renal function. Two patients currently are back on immunosuppression. The third recipient remains stable although off immunosuppression for 36 months; her cessation of immunosuppression was elicited by a mailed questionnaire sent to all recipients following detection of the first four. In addition to these five patients, three 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.