Penetration kinetics of 8-methoxypsoralen (8-MOP) into human skin have been investigated under in vitro conditions. The dependence of the resulting tissue concentration on time of penetration, drug concentration in the applied preparation and vehicle composition has been studied. Tissue concentration of the drug was found to increase with time of penetration; however, in both horny layer and epidermis, this increase was followed by a significant decrease in concentration, (after 100 to 300 min), although a large amount of unpenetrated drug was present on the horny layer surface at all times. In contrast to this, 8-MOP accumulated in the lower corium and subcutis and reached concentrations higher then those found in the upper corium and epidermis. This accumulation of the drug is a consequence of the in vitro conditions and its amount is proportional to that amount that under in vivo conditions would have been taken up by the capillary system. Penetration was dependent on vehicle characteristics and was found to increase with increasing polarity of the vehicle. The penetration was found to be directly proportional to the applied concentration; however, the percentage of the drug that actually penetrated was inversely proportional to the applied concentration.