A total of 127 haploidentical living-related transplants have been performed at our institution since March 1986. A donor-specific transfusion plus azathioprine protocol was used until July 1988 (n = 74) and a random transfusion (RT) protocol without AZA used thereafter (n = 53) in an effort to decrease risk of recipient sensitization and reduce the burden on the prospective donor. All patients were given cyclosporine 8 mg/kg/day orally beginning 1 week prior to transplantation. Immunosuppression was similar in both groups and consisted of triple induction therapy with prednisone, CsA, and AZA. A positive T cell crossmatch eliminated the potential donor. Seven individuals (9.6%) were sensitized in the DST group and 1 (1.9%) in the RT group, leaving 67 and 52 patients in the two groups of the study, respectively. Groups were similar with respect to age, sex, history of pregnancy in female patients, peak and baseline panel-reactive antibody (PRA), DR match, and prior transplants. The groups differed slightly with respect to AB antigens shared, with an advantage in the RT group. Actuarial graft survival was not statistically significantly different between the two groups, with 2-year graft survival of 95% in the DST and 91% in the RT group (log rank, P = 0.16). Patients in the RT group had significantly more rejection episodes and had them sooner than their counterparts in the DST group. At the end of 1 year, 50% of patients in the DST group had at least 1 rejection episode, compared with 75% of patients in the RT group (P = 0.0008). Multivariate (Poisson) analysis of 10 variables was performed, with an overall model P-value of 0.0001. Only DST (P = 0.0001) and pregnancy (P = 0.015) were significant predictors of rejection episodes, both protective. The difference in rejection episodes and the timing with which they occur has not yet translated into a significant difference in graft survival between DST and RT groups.