Abnormal photosensitivity of skin in the photosensitivity dermatitis/actinic reticuloid syndrome (PD/AR) correlating to an abnormal photosensitivity of dermal fibroblasts from these patients has been established previously. Cultured human skin fibroblasts from normal infant and adult donors, foreskin tissue and patients with PD/AR were assayed for oxidative stress induced membrane damage following ultraviolet A (UVA) radiation (340-450 nm) and hydrogen peroxide treatment by measurement of lactate dehydrogenase release. Skin fibroblasts from PD/AR patients were, in general, 2- and 4-fold more sensitive than normal controls regarding membrane-induced damage to UVA radiation and hydrogen peroxide treatment, respectively. Cells from one patient where biopsies were taken during full disease flair and 2 years later, following disease remission by immunosuppressive therapy, showed the same cellular sensitivity. In addition, fibroblasts from foreskin tissue were resistant to UVA radiation as measured by lactate dehydrogenase release, suggesting that this frequently used source of cell culture does not provide the best control group for comparison with photosensitive disease states. All these results suggest that the target for the cellular sensitivity seen in cells from PD/AR patients is the membrane