The receptor fluid used in an in vitro percutaneous absorption study should not only serve as a receptor for the penetrant but also preserve the viability of the skin. Lipophilicity of the receptor fluid plays a crucial role in facilitating the release of a lipophilic compound from skin into the receptor fluid. Until now, 4% bovine serum albumin (BSA) has routinely been added to HEPES-buffered Hanksł balanced salt solution (HHBSS) to increase the aqueous solubility of lipoidal compounds. Hydroxypropyl-ß-cyclodextrin (HPCD) was compared with BSA for its ability to solubilize lipid material and also maintain skin viability. Concurrent with the development of a more lipophilic receptor fluid, a second skin viability assay was evaluated as an alternative test to the lactate assay. Ultimately, the MTT (3-{4,5-dimethylthiazol-2-yl}-2,5-diphenyltetrazolium bromide) assay was shown to be a more accurate and reliable method for assessing skin viability than the lactate assay. HHBSS + 2% HPCD proved to be more suitable than HHBSS + 4% BSA. With HHBSS + 2% HPCD, better agreement was found between the results of in vitro and in vivo skin absorption studies of a fragrance ingredient and skin viability was maintained for the entire 24-hr study.