Recipients receiving marrow from donors other than HLA identical siblings (alternative donors) treated by monotherapy with either methotrexate (MTX, n = 5) or cyclosporin A (CSA, n = 10) were compared with 28 recipients of alternative donor marrow receiving MTX + CSA. The former group had a cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) of 73% compared with 34% in the latter group (p = 0.009). The incidence of chronic GVHD was 75% and 41% in the two groups respectively, a difference that was not statistically significant. Death caused by GVHD was 47% in recipients of alternative bone marrow treated with monotherapy vs 12% in those treated with MTX + CSA (p = 0.008). The actuarial 4-year patient survival was 7% and 46% in the two groups, respectively (p = 0.04). Compared with HLA identical siblings the recipients of alternative marrow treated with monotherapy had an increased risk of grade II-IV acute GVHD (p less than 0.0001), an increased death rate by GVHD (p = 0.0001) and a decreased survival (p less than 0.0001). When MTX was combined with CSA the recipients of alternative marrow had an increased risk of grade II-IV acute GVHD (p = 0.005), but death by GVHD (12 vs 6%) and 4-year patient survival (46 vs 45%) did not differ.