Recent advances in sensitive analytical techniques have enabled the analysis of drugs in unconventional biological materials such as sweat. In a study conducted during a heroin maintenance program, 14 subjects had sweat patches applied, then received intravenously two or three doses of heroin hydrochloride ranging from 80 to 1000 mg/day. The sweat patch was applied 10 min before the first dosage and removed approximately 24 h later, minutes before the next dosage. Absorbent pads were stored at -20 degrees C in plastic tubes until analysis. The target drugs were extracted in 5 mL of acetonitrile in the presence of 100 ng each of heroin-d9, 6-acetylmorphine-d3, and morphine-d3. After agitation for 30 min, the acetonitrile solution was divided into two portions: 2 mL for heroin testing and the remainder for testing for the other compounds. After evaporation, the residue of the first portion was reconstituted in 35 microL of acetonitrile; the second was derivatized by silylation with 40 microL of N,O-bis(trimethylsilyl)trifluoroacetamide containing 10 mL/L trimethylchlorosilane. Drugs were analyzed by GC-MS in electron impact mode. Concentrations (nanograms per patch) ranged from 2.1 to 96.3 for heroin, 0 to 24.6 for 6-acetylmorphine, and 0 to 11.2 morphine. Except in one case, heroin was the major drug present in sweat, followed by 6-acetylmorphine and morphine. We observed no correlation between the doses of heroin administered and the concentrations of heroin measured in sweat.