Six male and two female subjects participated in a clinical study to determine the time course, the cumulative excretion, the intrasubject variability, the influence of site application, and the concentrations of codeine or phenobarbital in sweat following administration of a single dose of the drug. The doses of codeine and phenobarbital were 90 and 100 mg. respectively. Sweat was collected by means of a Sudormed sweat patch. Patches were removed at specified times over 1 week, and the drug content was determined by gas chromatography-mass spectrometry using deuterated internal standards. Codeine was detectable at 1 h following the administration, and a plateau concentration was observed on the third day. The peak codeine concentration was observed during the 12-24-h period. Morphine was never detected in sweat. In contrast, phenobarbital was first observed 3 h after administration, and cumulative excretion was continual throughout the week. Intersubject variability was enormous, as the concentrations for the same dose were in a magnitude of 1-5. Concentrations were in the range of 2-127 and 0.5-33 ng per patch for codeine and phenobarbital, respectively. The influence of the site of patch application was evaluated by analysis of six patches, all removed at the same time (24 h) in two subjects receiving 90 mg codeine. Codeine concentrations differed by a magnitude of 1-3 according to the area of application: the upper arm, the back, and the ribs. These data suggest that the sweat patch technology can be useful for documenting drug use over a 1-week period of surveillance.