Methotrexate (MTX) followed by citrovorum factor (CVF) rescue was evaluated for its effectiveness in reducing graft-versus-host disease (GVHD) in lethally irradiated dogs transplanted with bone marrow from unrelated histoincompatible donors. Animals were given no immunosuppressive therapy (group A) or a combined regimen of MTX and CVF (group AMC). These two groups were compared with a group of animals transplanted earlier given MTX alone (group AM). Ainmals in the AMC group lived significantly longer than the A group (p less than 0.05). Engraftment rate, hematopoietic recovery and incidence of GVHD were similar in all three groups. Incidence of early deaths was significant in the AM group (p less than 0.05). It is concluded that MTX combined with CVF increases survival and is an effective posttransplantation immunosuppressive regimen with minimal toxicity.