Hairless mice were administered various amounts of 8-methoxypsoralen (8-MOP) by gavage, followed by irradiation with ultraviolet light (UVA) two or more times per week for periods ranging from 1 to 12 months. The minimum phototoxic dose was 20 mg/kg body weight by this route of administration and potential for serious organ toxicity in long-term exposures was investigated. No histologic features of cutaneous malignancy were encountered under test conditions which produced prolonged phototoxicity, deep ulceration, cicatrization, and other deformities. Repeated daily gavaged doses of 20 mg psoralen/kg body weight in conjunction with twice weekly irradiation for 10 min with UVA elicited an erythematous phototoxic reaction, but did not give rise to subsequent skin lesions. 8-MOP in repeated daily gavage doses of 30 mg and 40 mg/kg body weight combined with twice weekly UVA irradiation for 10 min caused severe burning with subsequent scarring, but did not induce malignant tumors in experiments lasting lasting 8 months. No organ toxicity was seen except for toxic liver changes when severe cutaneous burn and pronounced ulcerations were produced. Limited immunologic studies disclosed no abnormalities in this system.