Between September 23, 1968 and March 22, 1980, primary renal allografts were performed in 373 uremic patients with insulin-dependent diabetes. After transplantation 65 of the diabetic patients (17%) underwent 151 amputations involving at least a digit or a limb. The lower extremity was involved in 72% of the amputations. Twenty-four patients had only one procedure, while 41 required multiple procedures. Mean interval from transplantation to first amputation was 25.2 +/- 2.4 (SE) months. Patient and graft loss (perioperative risk) in the first 3 months after amputation was 13%. Diabetic renal allograft recipients living long enough to require amputation have more severe manifestations of vascular disease. These amputees display both an 11% lower patient and graft survival after the first year following transplantation, as well as an accelerated rate of graft loss following amputation. Those diabetics requiring an amputation do significantly more poorly than nonamputees of the corresponding demographic category if diabetes onset occurred at age 10 to 20 years, diabetes duration prior to transplant was less than 20 years, age at transplant was less than 30 years, dialysis duration was less than 4 months, and donor type was HLA-nonidentical related. Nevertheless, more than 50% of the diabetics undergoing amputation will be alive with functioning allografts 4 years after amputation. On the other hand, diabetics not requiring amputation do particularly well if they survive 1 year, with more than 80% chance that they will be alive with a functioning graft 4 years after transplantation.