Longwave ultraviolet radiation (UVA-32&400 nm) is known to induce inflammation, pigmentation and tumor production in mammalian skin. The mechanisms by which such radiation induces these biologic phenomena are poorly defined. In an effort to broaden our knowledge in this area, we examined the effect of UVA on DNA biosynthesis in Hartley strain albino guinea pig skin. The animals were irradiated with selected doses of solar simulated UVA, and DNA was assayed by [.3H]thymidine incorporation into epidermal DNA by autoradiography . These studies revealed that UVA inhibited DNA synthesis in a dose dependent manner between 40 and 80 J at 3 h postirradiation. This inhibition was followed by a stimulation of synthesis at 5 h and a second inhibition/ stimulation at 8 and 24 h, respectively. Although the mechanism of alteration is undefined, our data suggest that UVA has profound effects on DNA biosynthesis in mammalian epidermis.