Exposure of murine epidermal cells to UV radiation in vitro causes the release of immunoregulatory factors that mimic some of the immunosuppressive effects of in vivo UV irradiation. The purpose of this study was to investigate the spectrum of immune responses affected following i.v. injection of supernatants obtained from cultures of epidermal cells exposed in vitro to UV radiation. Treatment of primary epidermal cell cultures or transformed keratinocytes (Pam 212 cells) with UVB (280-320 nm) radiation caused the release of factors that suppressed the induction of delayed hypersensitivity to alloantigen and trinitrophenyl-modified self-antigens in syngeneic and allogeneic mice. Contrary to expectations, however, the injection of supernatants from UVB-irradiated epidermal cells had no effect on the induction of contact hypersensitivity to trinitrochlorobenzene. On the other hand, treatment of the keratinocytes with UVA radiation (320-400 nm, filtered to remove wavelengths in the UVB region) resulted in the release of a factor that suppressed contact but not delayed hypersensitivity. Neither the UVA-induced nor the UVB-induced suppressive factor inhibited the generation of an antibody response to sheep erythrocytes, indicating that, like the suppression that occurs after in vivo exposure to UV radiation, the suppression induced by factors from UV-irradiated keratinocytes is selective in nature. These data support the hypothesis that soluble keratinocyte-derived suppressive factors are involved in the induction of systemic immune suppression by UV radiation. In addition, they suggest that multiple suppressive factors, having different immunosuppressive properties, are produced by different wavelengths of UV radiation.