Sweat collection patches are used for drug abuse monitoring. We investigated the effect of sweat patch location (back and shoulder) on cocaine levels after controlled intravenous cocaine exposure (210 mg/70 kg) in 12 subjects (Experiment 1). Gas chromatographic-mass spectrometric analyses show cocaine and metabolites levels in Pharmchek trade mark patches were eightfold higher on the back than those on the shoulders. To assess the mechanisms for possible loss of cocaine from patches during wear, 48 sweat patches with a small amount of cocaine-d(5) (100 ng as base/patch) were placed on the backs of eight cocaine-naive volunteers for up to 72 h (Experiment 2). Drug-free patches were applied over eight of the cocaine-d(5) (100 ng) containing patches to measure loss through the patch. Cocaine levels in spiked patches declined over time (p = 0.002), with levels at 48 h postapplication 30% less than control, consistent with possible drug reabsorption. Cocaine was detectable (> 2 ng/patch, LOQ) in four of eight initially cocaine-free patches placed on top of the cocaine-containing patches, indicating transfer through the patch outer membrane. Conversion to benzoylecgonine was detectable but at low levels (< 2%). Reabsorption (back transfer), degradation or hydrolysis, and loss of cocaine to the environment may account for substantial loss of cocaine from skin sweat collection patches during patch wear.