We compare the expression of donor class I and class II major histocompatibility complex antigens in DA kidney grafts transplanted to PVG recipients treated by different protocols of donor-specific immunosuppression. MHC expression was evaluated using donor-specific antibodies and assays by immunohistology and quantitative absorption analysis. PVG recipients were either untreated or treated by (A) twice-weekly intravenous injections of 0.5 ml DA blood for 12 weeks; (B) 0.5 ml DA blood intravenously at 7 days pregraft; (C) as for (B), but with the addition or oral cyclosporine at 10 mg/kg/day from the day of grafting; and (D) passive enhancement with DA anti-PVG serum. Grafts were assessed at 3, 5, and 7 days after transplantation. In untreated controls at day 3, there is a periarteriolar leukocyte infiltrate, weak or absent class II induction, but strong class I induction. Class II induction in untreated controls is maximal at day 5. We confirm that active enhancement by blood transfusion, even using the intensive protocol of twice-weekly transfusions for 3 months, results in accelerated leukocyte infiltration and accelerated donor class I and class II MHC induction. At day 3, there is an intense, diffuse leukocyte infiltration and maximal class II induction. Cyclosporine treatment of blood-transfused recipients reduced the leukocyte infiltration and MHC induction to levels seen in untreated controls—i.e., the accelerated MHC induction caused by the transfusion was partially reversible by cyclosporine. In passively enhanced recipients, leukocyte infiltration and class I MHC induction were similar to untreated controls. However, class II induction was much delayed, not being evident until day 7.