During the 7-year period from March 1984 to June 1991, 86 haploidentical living related kidney recipients were entered into one of three donor-specific transfusion (DST) and cyclosporine treatment protocols: (1) Multiple pretransplant DSTs with cyclosporine begun after transplant, n = 34; (2) Multiple pretransplant DSTs with cyclosporine begun pretransplant, n = 31; and (3) a single DST 24 to 48 hours before transplant with intravenous cyclosporine initiated after the transfusion, n = 21. Triple immunosuppression (prednisone, azathioprine, and cyclosporine) was continued in all groups after transplant. The 1-year patient (97%, 97%, and 93%, p = not significant) and graft (91%, 90%, and 87%, p = not significant) survival were similar for the three groups. No differences were seen in the incidence of rejection at 1 year (61%, 45%, and 60%, p = not significant) or in the incidence of infectious complications (26%, 42%, and 47%, p = not significant). It is concluded that a single DST given 24 to 48 hours before operation followed by pretransplant cyclosporine is as effective as classic DST conditioning of recipients using either pretransplant or post-transplant cyclosporine. The single DST protocol has the advantage of not eliminating any donors because of sensitization and was less costly and easier to administer.