The effects of therapy with four commonly used immunosuppressants--azathioprine, prednisolone, cyclophosphamide, and cyclosporine, on (UVI)-induced skin carcinogenesis were studied in the albino hairless (HRA/Skh-1) mouse. Following 30 weeks' exposure to UVI (290-400 nm) alone, 87% of mice developed skin tumors; the mean incidence of tumors at that time was 2.4 per mouse; and the tumors were predominantly papillomas (72%), with the remainder being carcinomas (25%) and keratoacanthomas (3%). Mice received immunosuppressive drug therapy beginning shortly after the start of UVI and continuing for up to 28 weeks. All drugs were given at immunosuppressive levels and dosages were comparable on a body weight basis to those used in clinical transplantation. Prednisolone had no effect on UVI-induced tumor development. Cyclosporine caused a moderate reduction in the latent period for tumor induction. Azathioprine and cyclophosphamide had strong promoting effects; the latent period for tumor induction was shortened and the tumor yield per mouse was increased (4.3 and 5.7 tumors per mouse, respectively, at 30 weeks after the start of UVI). Azathioprine, but not cyclophosphamide, also induced a larger proportion of carcinomas (43% and 15%, respectively). The results suggest that for kidney transplant recipients treated with the standard immunosuppressive drug regimen of azathioprine/prednisone, the increased susceptibility of the sun-exposed skin of these patients to squamous cell carcinoma is likely to be contributed to by specific promotion by the azathioprine therapy of the carcinogenic effects of sunlight.