Graft survival rate was evaluated in 61 recipients with greater than 50% of preformed antibodies to selected panel cells. This includes recipients of primary cadaver grafts, secondary cadaver grafts and living related grafts. Graft survival rate also was evaluated in 199 recipients with pretransplant antibodies reacting with 10-50% of panel cells and in nonsensitized patients. Good graft survival can be obtained in many hyperimmunized patients, particularly in recipients of primary renal allografts (66% cadaver graft survival rate at 2 yr). Sensitization following rejection of an allograft appears to confer a less favorable prognosis. The nature of recipient presensitization and the precise specificity of each reactivity cannot always be explained. This is exemplified in 3 patients in whom broadly reactive lymphocytotoxic antibodies were not directed against HL-A antigens. Since the number of sensitized patients who await renal transplantation is increasing, there should be no hesitation in proceeding with transplantation, particularly with primary grafts. Emphasis must be placed on frequent prospective recipient serum sampling so that transient high levels of cytotoxin do not escape detection and can be easily selected out for cross-matching against potential donors.