Melphalan has rarely been used as a single agent for conditioning prior to allogeneic marrow transplantation. Twenty-eight patients (median age 19.5 years) undergoing allogeneic BMT for acute leukemia (n = 26) or lymphoblastic lymphoma (n = 2) in first remission (n = 10) or beyond (n = 18) from HLA-identical siblings received 240 mg/m2 melphalan. Death due to primary graft failure was seen in two patients. Sustained hematopoietic recovery was seen in all the others (n = 22) not dying early due to toxicity (n = 2) or persistent active disease (n = 2). The 3-year probabilities of transplant-related mortality and relapse were 35% and 62%, respectively. Seven patients are alive and well at 103-163 months (median 136) with Karnofsky scores of 100% (10-year disease-free survival, 25%). Of the 16 patients with donors of the opposite sex, seven underwent cytogenetic studies after BMT and showed complete chimerism with donor cells. Amongst the four women who were 15-30 years at the time of the transplant, there were seven pregnancies over 297 months of follow-up beyond 2 years from transplant. In contrast, no pregnancies were seen in 53 women with hematologic malignancies who were conditioned with other regimens over 3524 months of follow-up beyond 2 years from transplant. The pregnancy rate was significantly higher (P < 0.001) for women conditioned with melphalan alone (three of four) than for those conditioned with other regimens (0 of 53). We conclude that pre-transplant conditioning with melphalan alone permits alloengraftment of marrow from HLA-identical siblings, and may preserve fertility better than other regimens in some women.