In vitro skin penetration rates in rat and man were compared to those obtained in vivo in rats. Saturation of absorption was frequently observed at higher exposure levels in in vitro and in vivo. Lipophilic compounds showed the highest penetration rates through rat skin in vitro. In all cases in vitro dermal penetration through rat skin was higher than in vivo. Thus, the in vitro study may serve as a first tier test. The in vivo data suggest an inverse relationship between molecular weight and the rate of dermal absorption for lipophilic as well as hydrophilic compounds. Rat skin was more permeable to all tested substances than human skin (mean difference 10.9-fold). Thus, the systemic exposure of humans may be significantly overestimated if risk assessment is based only on the results of an in vivo rat study, because human skin is less permeable than rat skin. It would appear, therefore, that an estimate of actual dermal penetration through human skin should be based on the combined use of in vivo and in vitro data, using the following equation: % Human dermal penetration = (% rat in vivo dermal penetration) x (in vitro rate dermal penetration human / in vitro rate dermal penetration rat).