Continued prospective study of the 1,380 patients enrolled in the PUVA study for 10 years after first exposure to PUVA demonstrates a strong association between cumulative exposure to PUVA and an increased risk of squamous cell carcinoma of the skin. For tumors occurring at least 58 months after first treatment, after adjustment for age, sex, and area of residence, we observed that patients with more than 260 treatments had an 11-fold increase in risk compared to patients who had received 160 or fewer treatments during the same interval (P less than 0.01). Comparable increases in relative risk were noted in patients of all skin types, irrespective of prior ionizing radiation exposure. We also noted a modest dose-dependent increase in the risk for the development of basal cell carcinoma for patients who received an excess of 200 treatments compared to those who had received fewer than 160 treatments within the same time period (P less than 0.05). Tumors detected in our cohort exhibit biologic behavior similar to non-melanoma skin cancers associated with sun exposure. Careful monitoring and early detection should limit the morbidity associated with these tumors.