Lethally irradiated rhesus monkeys were used in studies of allogeneic bone marrow transplantation. Animals given doses in excess of 812 rads survived an average of 11.7 days. Long-term survival was obtained in monkeys similarly irradiated and given autologous bone marrow cells. Irradiated monkeys given allogeneic marrow developed acute lethal graft-versus-host (GVH) disease with a mean survival time of 9.1 days. Eleven monkeys received allogeneic bone marrow following treatment with antilymphocyte serum (ALS) and lethal irradiation. Monkeys receiving ALS prepared in horses had less severe and less rapidly progressing GVH disease than untreated recipients. ALS prepared in rabbits was even more effective in preventing the acute GVH reaction and allowed survival times of up to 43 days. ALS-treated monkeys developed a subacute or chronic wasting syndrome which was clinically distinct from the severe acute GVH disease seen in unmodified allograft recipients. In addition, ALS-treated animals had prolonged depression of peripheral lymphocyte counts following transplantation in contrast to unmodified recipients which developed an early rise in circulating lymphocytes. It appears that ALS may act either upon donor immunocompetent cells and their precursors at the time of transplant or it may react with host-type cells which are the targets of donor immunocompetent cells. By the use of ALS, a primate model of subacute and chronic GVH disease can be produced which is suitable for studies of the mechanism and pathophysiology of the primate GVH reaction. The effectiveness of ALS in modifying acute primate GVH disease also suggests that further clinical trials of ALS in marrow transplant recipients are indicated.