Human brain tissue was sectioned at autopsy, and samples were subjected to lipase digestion, subsequent to solid phase extraction. One-gram samples of brain tissue were homogenized with 2 ml of 0.2M Tris buffer adjusted to pH 6.3 with orthophosphoric acid. One milligram of triacylglycerol lipase was then added, together with bupivacaine as the internal standard. Following incubation for 2.5 hours at 50 degrees C, drug-free brain homogenates were spiked with various concentrations of cocaine prior to enzymatic digestion to ensure that the digestion process had no effect on drug stability. The distribution of cocaine and benzoylecgonine throughout different regions of the brain was determined by high-performance liquid chromatography (HPLC). The HPLC system gave a good separation of cocaine and its metabolite benzoylecgonine. The concentrations of cocaine found in the brain were generally four to eight times greater than that found in the blood. The absence of large concentrations of benzoylecgonine supported previous reports of cocaine stability in the brain. 8 references, 1 table, and 1 figure (Author abstract modified)