T cell depletion of donor bone marrow prevents graft-versus-host disease (GvHD) but increases the risk of rejection. Rabbit bone marrow was T-cell-depleted using the properties of rabbit T cells to form spontaneous rosettes in the cold and by incubation in methylprednisolone (1 mg/ml, 10(6) cells/ml). New Zealand white rabbits were transplanted with Red Burgundy rabbit bone marrow from the opposite sex after conditioning with 12 Gy total body irradiation. Untreated animals die of GvHD at day 23. Three groups were studied: T cell depletion plus ciclosporin (A), T-cell-depleted bone marrow plus irradiated autologous bone marrow plus irradiated donor buffy coat (B), and T-cell-depleted bone marrow plus irradiated autologous bone marrow plus irradiated donor buffy coat plus ciclosporin (C). Buffy coat cells irradiated with 15 Gy were given for 5 days. Such cells do not form colonies in culture; however, they are able to release interleukin-2. In group A, 9 of 15 animals rejected, 6 survived for 45 days (median, range 16-249 days). In group B, all 5 of 5 animals died of rejection (median survival time 14 days, range 13-20 days). In group C, 8 of 10 animals did engraft, 4 died of GvHD (median survival 48 days, range 26-58 days), and 4 are long-term survivors (greater than 6 months to greater than 1 year), 3 as complete chimeras. We conclude that the combination of irradiated donor buffy coat cells, irradiated autologous bone marrow and ciclosporin restores engraftment of T-cell-depleted mismatched bone marrow without losing the benefit of reduced GvHD.