The aim of this study was to determine whether or not the skin acts as a reservoir for cocaine. Cocaine-d5 (1 mg/kg) was administered to five nondependent, cocaine-experienced volunteers. Skin tissue, interstitial fluid, sebum, stratum corneum, and plasma were collected for 72 h after drug administration. Cocaine and benzoylecgonine (BE) levels were determined using GC-MS. Cocaine concentrations peaked in plasma at 1 h after administration, with pharmacokinetic parameters (t(1/2), CL, Vd) also in the expected ranges. In skin, cocaine levels peaked around 1.5 h after administration and became undetectable by 6 h. A correlation was found between the plasma and skin AUC for cocaine (R = 0.99, p = 0.006, N = 4). BE was not detected in skin. In interstitial fluid (N = 4), cocaine concentrations peaked around 5 h after drug administration and were undetectable by 24 h. BE peaks varied between 2 and 24 h and were not detectable at 48 h. In sebum, cocaine levels peaked between 3 and 24 h. BE was found in three samples between 12 and 24 h. In stratum corneum, cocaine was measurable in only one sample from one subject. These findings suggest that skin does not act as a reservoir for cocaine. Rather, cocaine appears to be distributed rapidly to the skin and eliminated, following a time course similar to that of plasma.