Laboratory tests to assess the irritant potential of materials, such as skin cleansers, which are normally used over a long period by humans, fail to mimic actual use. Most washing tests last a few days or at most a few weeks. Skin sites and techniques are often not standardized. The more standardized patch test involves occlusion and results in exaggerated reactions, since even water and blank patches produce visible and pathophysiologic changes. All of these tests rely on visual assessment despite strong evidence that similarly appearing skin can be very different histologically. The primary objective of this study was to use a well-defined animal model to evaluate the cumulative effects of repeated skin exposure to low levels of surfactants of varying skin irritation potential. A secondary aim was to examine whether or not surfactant-induced skin changes were exacerbated by suberythemal UV radiation. Test materials were applied topically, 2× daily to the dorsal areas of normal and low-dose solar simulator exposed mice for 15 weeks. Our results show that, with conditions mimicking typical normal use, these surfactants and skin cleansers produce little or very mild histological changes in the skin. UV irradiation alone produced the greatest change in all histological parameters examined, with no synergistic or additive effects with the topical treatments.