Previously we reported that exposure of mice to UV radiation increases the incidence of melanomas arising from injection of syngeneic melanoma cells into the UV-irradiated ears. In this study, we investigated the UV dose-response characteristics, duration, waveband dependence, and role of inflammation in this effect of UV irradiation. The optimal conditions consisted of short term (3-4 weeks), intermittent (twice weekly) exposures to a moderate dose (4.8 kJ/m2) of UVB (280-320 nm) radiation from FS40 sunlamps and the effect lasted only for 3 days after the final UV irradiation. Removal of wavelengths below 315 nm with a Mylar filter abrogated the effect. The UV dose response and the time course of UV-induced inflammation, assessed by ear swelling and microscopic evaluation, did not correlate with that for enhanced melanoma outgrowth, nor did the treatment of the ears with the inflammatory agents turpentine and 12-o-tetradecanoyl phorbol-13-acetate mimic the UV effects on melanoma development. These results indicate that enhancement of melanoma development in UV-irradiated skin is probably unrelated to the inflammatory effects of UV irradiation.