SUMMARYRecent reports indicate that L-asparaginase may affect the normal function of immunologically competent cells and/or their precursors and may prolong the survival of skin allografts and heterografts in mice and rabbits. In the present study, 31 mongrel dogs received renal allografts from randomly selected donors. They were treated with 150-200 international units of crystalline L-asparaginase/kg/day for 9-21 days after transplantation, and the results were compared with 79 control renal allografts performed without treatment in the same population. The mean survival time (MST) of renal allografts in L-asparaginase-treated animals was 15.64 ± 7.39 days; 3% of the transplants were rejected by the 9th day, and 32% survived for more than 16 days. The longest survival was 43 days. In contrast, the MST of the control allografts was 10.81 ± 3.38 days; 40% of the transplants were rejected by the 9th day, and only 5% survived for more than 16 days. The longest survival was 25 days. The prolonged renal allograft survivals observed in L-asparaginase-treated animals were associated with morphological evidence of a slowing of the allograft rejection response, with decreases in the intensity of the cellular infiltrates (which consisted mainly of macrophages) and with a paucity of lymphocytes. A number of histological changes compatible with a chronic type of renal allograft rejection were observed in these recipients. The results suggest that L-asparaginase may merit further consideration with regard to its possible usefulness as an immunosuppressive agent in renal transplantation.