We had reported previously that the outgrowth of melanoma is enhanced when melanoma cells are injected into UV-irradiated skin of syngeneic mice. To determine whether this effect was specific for melanomas, we compared the growth of 13 different tumor cell lines (3 melanomas, 6 fibrosarcomas, 2 undifferentiated skin tumors, a squamous cell carcinoma, and a spontaneous hepatocarcinoma) in UV-irradiated and nonirradiated syngeneic mice. C3H/HeN(MTV-) mice were exposed to 4.8 kJ/m2 UV-B (280-320 nm) radiation twice a week for 3 weeks; the tumor cells were injected into the UV-irradiated pinna 24 h after the final UV irradiation. The growth of all the melanomas and 4 of the fibrosarcomas was enhanced in UV-irradiated mice, indicating that the effect of UV radiation was not specific for melanomas or tumors of a particular etiology. Using an in vivo immunization and challenge assay, we found that the 7 tumors exhibiting enhanced development in UV-irradiated skin were highly immunogenic, whereas the remaining 6 tumors were not. This suggested that enhanced tumor outgrowth resulted from an immunosuppressive effect of the UV radiation. When tested further, we found that UV-B radiation had no effect on melanoma outgrowth in congenitally athymic mice, sublethally X-irradiated mice, or mice depleted of Thy1+ cells in vivo. These results indicate that immunological mechanisms play a role in the effect of UV radiation on the growth of murine melanomas.