Spotaneous E rosette-forming (T) lymphocytes were monitored in the peripheral blood of rhesus monkeys receiving a 5-day course of rabbit anti-human thymocyte globulin (RATG) after skin allotransplantation. Mean graft survival in RATG-treated recipients was 32.3 +/- 7.6 (SD) days compared with 8.2 +/- 1.7 (SD) days in controls. The percentage and total number of circulating T cells fell precipitously after RATG treatment and recovered slowly. Linear regression analysis showed that the recovery pattern of the total number of circulating T cells, but not the percentage of T cells, was significantly correlated with rejection. Specific antihuman T cell antibody was detected in RATG preparations after extensive absorption with human erythrocytes, platelets, and B lymphoblastoid cells. The cytotoxic titers of B cell-absorbed RATG preparations to human peripheral blood lymphocytes showed a significant correlation with the mean skin allograft survival times obtained in RATG-treated primates. Overall the data suggest that the immunosuppressive potency of RATG in the primate skin graft assay is related in large part to its anti-T cell activity.