The absorption of a model hydrophilic compound (benzoic acid) and a model lipophilic compound [di(2-ethylhexyl)phthalate; DEHP] was measured through separated epidermal membranes and through the residual stripped dermis of rat skin. Absorption was determined using both phosphate buffered saline (PBS) and 50% ethanol/water as the receptor fluid. The rate and extent of DEHP absorption through epidermis was greatly increased (40- to 80-fold) using 50% ethanol/water as receptor fluid compared with using PBS, but with the stripped dermis only a small difference (approximately two- to threefold) was detected. The use of 50% ethanol/water as receptor fluid also promoted the penetration of benzoic acid through the epidermis, but only to a limited extent (two- to threefold increase). As with DEHP, the penetration of benzoic acid through the dermis was also increased. The permeability to (3)H(2)O of epidermal, but not dermal membranes was also increased by the use of a 50% ethanol/water receptor fluid. It was concluded that 50% ethanol/water can increase the permeability of rat skin strata to both lipophilic and hydrophilic compounds. Further work is needed to provide a basis for selecting suitable receptor fluid formulations for in vitro dermal absorption studies.