The effects of ultraviolet irradiation (UVI) (290-400 nm) and/or systemic immunosuppressive drug therapy (azathioprine and prednisolone) on the immunocompetence of the skin of hairless (HRA/Skh-1) mice were investigated. Mice were studied for the density of ATPase+, Ia+ and Thyl X 2+ cells in the dorsal epidermis and contact hypersensitivity (CH) of skin to dinitrofluorobenzene (DNFB). Prednisolone therapy alone and UVI alone each reduced the densities of the three skin immune cell markers and CH responsiveness; azathioprine therapy alone had no such effects. When a suberythemal dose of UVI that induced a moderately depressive effect on these two skin parameters was used, additional azathioprine therapy produced no further depression; additional prednisolone therapy further depressed the densities of ATPase+ and Ia+ cells and CH responsiveness; additional therapy with combined azathioprine and prednisolone induced profound depression of the incidences of the three immune cell markers and of CH responsiveness. These data point to interaction between azathioprine/prednisolone therapy and UVI in depressing local immune function within skin which may contribute to the increased susceptibility of the sun-exposed skin of immunosuppressed kidney transplant recipients to infective and carcinogenic processes.