To document and quantify inducible photoprotective effects in human skin, explant cultures were treated once with thymidine dinucleotide (pTT) or diluent alone or UV-irradiated. Both pTT and UV increased the melanogenic protein levels on days 1-5 and comparably increased melanocyte dendricity and epidermal melanin content. Explants treated with pTT or UV but not with diluent alone showed initial inhibition of epidermal proliferation followed by mild reactive hyperplasia; melanocyte proliferation was minimal. To determine whether pTT and UV provide comparable protection against subsequent UV-induced DNA damage, explants were pTT- or diluent-treated or UV-irradiated. All explants were then irradiated with the same UV dose 72 hours later. Compared to diluent alone, pTT or UV pretreatment decreased the number of epidermal cells positive for cyclobutane pyrimidine dimers (CPDs) 50% immediately post-irradiation. In pTT- and UV- versus diluent-pretreated explants, the rate of CPD removal was also more rapid, approximately 80 vs 45% of the initial burden within 72 hours. These data confirm and quantify comparable SOS-like responses in human skin after pTT or UV irradiation, attributable to both increased epidermal melanin and increased DNA repair rate, in the case of pTT in the absence of initial damage.