Data from 634 patients who received HLA-identical bone-marrow transplants for acute lymphoblastic leukaemia in first or second remission were analysed to examine the influence of mode of prophylaxis against graft versus host disease on rate of relapse of leukaemia. Methotrexate was associated with a significantly lower risk of leukaemia recurrence than were other methods of GVHD prophylaxis (relative risk 0.2, p less than 0.0003, for first-remission transplants; relative risk 0.3, p less than 0.0001, for second remission transplants). The decreased risk of relapse did not seem to be mediated via an impact on incidence or severity of graft versus host disease. A direct antileukaemia effect of methotrexate is the most likely mechanism.