We investigated the capacity of three sunscreen compounds to protect mice from the inflammatory and immunosuppressive effects of ultraviolet radiation (UVR). The sunscreen preparations contained 7.5% 2-ethylhexyl-p-methoxycinnamate, 8% octyl-N-dimethyl-p-aminobenzoate, or 6% benzophenone-3 in an oil-in-water emulsion. Skin swelling was used as the measure of their effect on UVR-induced inflammation, and immunosuppression was assessed by contact sensitization with 2,4-dinitrofluorobenzene applied to UV-irradiated skin (local suppression) or a distant site (systemic suppression). The sunscreens were applied to the shaved dorsal skin of C3H mice, which were then given a single dose of UVR ranging from 2 to 32 kJ/m2 within the UVB (280-320 nm) region. All three sunscreens gave complete protection against local suppression of contact hypersensitivity caused by a dose of 2 kJ/m2 UVB. They also protected against both inflammation and systemic immunosuppression caused by UVR; however, protection was highly dependent on the UVR dose. Furthermore, the sunscreens were less effective in protecting against systemic immunosuppression than against inflammation. These results indicate that immunosuppression is less sensitive to the protective effects of the sunscreens than inflammation and that protection against UVR-induced inflammation does not necessarily imply prevention of immunologic alterations. In addition, these studies suggest that UVR-induced immunosuppression and inflammation may involve different mechanisms.