The purpose of this study was to optimize in vitro experimental conditions for the measurement of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) permeation across human skin using a flow-through diffusion cell system. The drug permeation rates through intact and stripped (stratum corneum (SC) removed) skin were also compared in order to determine if the SC provided significant resistance to the diffusion of hydrophobic Delta(9)-THC. The receiver fluids evaluated were HEPES-buffered Hank's balanced salt solution (HHBSS) with either 4 or 6% bovine serum albumin (BSA), Polyoxyethylene 20 Oleyl Ether (Brij 98) solution (0.5 and 6.0%), and hydroxypropyl-beta-cyclodextrin (HPBCD). The Delta(9)-THC permeability was significantly higher into Brij 98 solutions than into 4% BSA. BSA 6% receiver solutions showed significantly higher Delta(9)-THC permeation over BSA 4%. There were no significant differences in Delta(9)-THC permeability or lag time values between 0.5 and 6% Brij 98 receiver solutions. HPBCD failed to work as a suitable receiver solution. The Delta(9)-THC flux in the stripped skin experiments exceeded the flux in the intact skin experiments. It appears that the SC provides some resistance to the diffusion of Delta(9)-THC across human skin. These experimental results have confirmed the utility of several receiver solutions for the in vitro human skin diffusion study of Delta(9)-THC.