This study was carried out to determine the possibility of estimating drug concentration profiles in skin via a diffusion model. In an in vitro permeation study using butylparaben as model drug, percent of drug permeated amounted to approximately 57% and 76% for intact and stripped skin respectively, suggesting that the drug itself highly permeated through the stratum carneum. On the other hand, in vivo absorption study revealed that concentration of butylparaben decreased with skin depth where the maximum was achieved at approximately 30 rain and thereafter decreased gradually with time. In order to analyze both in vitro and in vivo percutaneous drug absorptions, Laplace transformed equations were derived based on four different kinds of hypothetical diffusion models. Initially, diffusion and partition parameters for butylparaben was calculated by curve-fitting using nonlinear regression program combined with a fast Laplace transform algorithm (MULTI(FILT)). Using these parameters, further simulation studies of in vivo drug concentration profiles were carried out. When washout process due to blood flow was not taken into consideration, the decline of drug concentration profiles could hardly be stimulated. However, when model considering washout process to have occurred at the specific range in the dermis (50-200 μm from the stratum carneum/dermis boundary), this could fit the actual concentration profiles of butylparaben in skin well. Thus, this study demonstrated that the diffusion model enables us to evaluate the in vivo behavior of drug in skin. © 1997, THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM. All rights reserved.