Focal dystrophy of epidermal cells, which was initially reported in 19 of 37 patients with psoriasis who had been treated with psoralen and ultraviolet A (PUVA), has now been observed in more than half of 70 patients 1 year or more following onset of PUVA therapy. These dystrophic changes, which are similar to those found in actinic keratoses, were present in clinically uninvolved skin of sunlight-protected and sunlight-exposed areas. Control biopsies obtained prior to PUVA therapy of non-sun-exposed skin in 62 patients and sun-exposed skin of 22 of these revealed no such changes. The presence of epidermal dystrophic changes in 9 patients who had a several-month interruption in PUVA therapy indicates that these changes cannot all be attributed to acute effects of PUVA. In 104 PUVA-treated patients returning for dermatologic follow-up after the first year of therapy, 17 (16.3%) developed actinic keratoses during the course of, or following the cessation of, treatment with PUVA. Careful examination of these patients prior to PUVA therapy had revealed no such lesions. In the majority of patients, keratoses were multiple; they occurred in sun-exposed areas, suggesting a possible acceleration or promotion by PUVA of actinically induced lesions.