The clinical outcomes of unrelated and of family related allogeneic bone marrow transplantation (BMT) were correlated with HLA disparity in a study in which molecular phenotyping of HLA-C was performed for unrelated donor-recipient pairs. The study included 30 patients who underwent BMT from unrelated donors and 43 patients who underwent BMT from family related donors. The unrelated group included 14 full match pairs, 12 class-I-C (molecular HLA-C) mismatched pairs, and 4 haploidentical pairs. The family related group included 9 full match pairs, 19 class-I mismatched pairs, and 15 haploidentical pairs. In the unrelated BMT group, the transplant-related complications of mortality, graft-versus-host disease (GVHD), and graft rejection, were significantly higher in molecular HLA-C mismatched than matched patients (67% vs 14%, P < 0.02; 50% vs 7%, P < 0.02; 42% vs 0, P < 0.02). The actuarial survival and the disease free survival (DFS) at 18 months was better for molecular HLA-C matched than for HLA-C mismatched unrelated transplants: 33% vs 18% (P = 0.065, NS), and 29% vs 16%, respectively. For the family related BMT group, the actuarial survival at 18 months was significantly higher for patients who were fully matched compared to those who were class-I mismatched, or those who were haploidentical pairs: 67%, 37%, and 13% respectively (P < 0.02). The actuarial DFS at 18 months of patients who were fully matched and of those who were class-I mismatched was similar, and better than that of haploidentical patients 45%, 37% (NS) and 13% respectively (P < 0.045). A lower incidence of transplant-related mortality occurred in class-I mismatched, family related (37%) than in locus-C mismatched unrelated patients (67%), and no difference was observed in the fully matched family related and unrelated patients. We conclude that a mismatch in locus C may be detrimental to BMT outcome and should therefore be included as a risk factor in the routine pre-BMT HLA phenotyping.