The interactions between antilymphocyte serum (ALS) and cyclosporin A and between enhancing serum and cyclosporin A were investigated in a DA to Lewis rat renal allograft model. Subtherapeutic doses of cyclosporin A (2 mg/kg/day), when combined with enhancing serum, produced no consistently beneficial effect in animal survival. A short course of cyclosporin A in therapeutic doses (5 mg/kg/day for 4 days) with enhancing serum was also no better than either agent used alone in prolonging rat survival. Subtherapeutic doses of ALS along with subtherapeutic doses of cyclosporin A (2 mg/kg/day) showed a favorable interaction, prolonging animal survival to a median of 59 days. Combination of immunosuppressive agents did not improve the histological picture of allograft rejection when compared to that seen when the agents were used individually. That cyclosporin A plus ALS show a favorable interaction, whereas cyclosporin A plus enhancing serum does not, may indicate that cyclosporin A and enhancing serum operate on the same portion of the immune response.