To assess the effect of related versus unrelated donors on outcomes in patients following T-cell-depleted (TCD) allogeneic BMT, we compared engraftment, GVHD, relapse rates, and survival in BMT patients who received CD6+ TCD marrow from HLA-matched related donors (MRD) with those in patients who received CD6+ TCD marrow from unrelated donors (URD). A total of 170 consecutive patients (120 with related donors, 50 with unrelated donors) were analyzed. The 2 groups were similar in age, sex, prior cytomegalovirus exposure, and stage of disease at the time of transplantation. GVHD prophylaxis was identical in the 2 groups, with TCD as the only method of GVHD prophylaxis. The total number of nucleated, CD34+, CD33+, and CD6+ cells infused did not significantly differ between the 2 groups. The median day to reach 500 x 10(6) neutrophils/L was 12 days for both related (range, 8-22 days) and unrelated (range, 9-23 days) graft recipients (P = .92). Incidence of grades 2 through 4 acute GVHD was higher in URD than in MRD recipients (42% versus 20%, P = .004). According to multivariable analysis results, donor source was the single most important factor influencing GVHD (P = .01). The 2-year estimated risk of relapse was 45.9% in MRD recipients compared to 25.7% in URD recipients (P = .06). Multivariable analysis revealed that the 2 most pertinent factors adversely affecting overall survival were advanced disease stage (P = .0002) and age greater than 50 years (P = .0003) at transplantation. There was no difference in relapse-free survival in URD and MRD recipients. We conclude that for patients undergoing TCD-BMT, use of unrelated marrow is associated with a higher risk of GVHD and other transplantation-related complications. However, these adverse events do not lead to inferior probability of relapse-free survival because they are accompanied by a reduction in relapse rates.