Sunscreen preparations can reduce the erythemogenic ( sunburning ) effects of solar ultraviolet radiation (UVR). Less is known about the ability of sunscreens to protect against other forms of UVR-induced damage. This study was designed to yield data on epidermal cell damage at UVR doses sufficient to provoke vascular changes (edema and erythema) in hairless mice, and to determine the comparative effectiveness of a commercial sunscreen in protecting against these two criteria of injury. The sunscreen (Piz Buin 12 Sun Protection Cream) was used at full concentration and at three serial dilutions. The dorsa of 144 hairless mice were treated with one of six sunscreen or vehicle preparations and subsequently irradiated with one of six exposures to an appropriately filtered xenon arc solar simulator. Vascular responses were determined by observing the animals for alterations in the gross appearance of the treated and irradiated sites (edema and erythema). Epidermal cell damage was assessed by determining the sunburn cell ( SBC ) indices in the epidermis removed 24 hours after irradiation. Both the vascular responses and SBC indices indicated that the sunscreen provided concentration-dependent protection against radiation damage. Furthermore, SBC indices provided a relatively continuous variable for quantification of sunscreen effectiveness.