Frequencies of spontaneous and radiation-induced chromosome aberrations were documented in lymphocytes from patients with basal cell nevus syndrome (BCNS) and from those with epidermodysplasia verruciformis (EV). Cells were irradiated with single or double doses of gamma-rays or UV light. For the double dose irradiation protocol, the two doses were separated from each other by 60 min. After irradiation of cells with 4 or 2 + 2 J/m2 UV light, lymphocytes from seven BCNS patients had a similar number of aberrant cells compared with normal controls, while cells from three EV patients showed a significantly increased number of cells containing aberrations, particularly chromatid-type aberrations, compared to controls (p < 0.03, Student's t-test). Similar results were observed whether the cells were irradiated with single or double doses of UV light. In addition, lymphocytes from EV patients had significantly lower mitotic indices than controls whether the cultures were irradiated with UV light or unirradiated (p < 0.05; Student's t-test). After irradiation with 100, 100 + 100 or 50 + 50 cGy gamma-rays, the mean chromosome aberration frequencies from nine BCNS patients and two EV patients were not significantly different from the controls. The spontaneous chromosome aberration frequencies were similar for the patients and the controls. Our data indicate that BCNS and EV lymphocytes irradiated with gamma-rays have a normal DNA repair response. However, cells from EV patients have an abnormal repair response to UV light induced DNA damage. This abnormality is probably caused by deficiency in DNA repair and it is consistent with the patients' sensitivity to UV light induced cutaneous squamous cell carcinomas.