A clinical therapy for psoriasis, a hyperproliferative disease of the skin, utilizes topical application of crude coal tar sometimes followed by UV irradiation (Goeckerman therapy). To investigate the formation of covalent DNA adducts resulting from this therapy, skin biopsies were obtained from treated patients and controls. Indirect immunofluorescence staining with antisera generated against benzo(a)pyrene diol epoxide-modified DNA was used to investigate cell-specific localization of adduct formation. Specific nuclear staining was detected in the epidermal cells of all biopsies from treated patients but not from control biopsies obtained from untreated individuals. 32P postlabeling of DNA isolated from the biopsies was used to determine the spectrum of hydrophobic adducts present. A pattern of multiple adducts was detected in the samples obtained from the treated patients but not from controls.