The SFE behavior of cocaine and its primary metabolite benzoylecgonine was studied and found to be highly dependent on the nature of the matrix and the manner in which the target drug analytes were incorporated into or on the matrix. The dependence of extractability on hair/drug binding interactions allowed the differentiation of cocaine present at different discrete sites in hair based on differences in SFE behavior, suggesting the potential for distinguishing exogenous (i.e., environmental) from endogenous (i.e., physiological) sources of drugs in hair by using sequential extraction under differing SFE conditions. SFE using pure carbon dioxide was found to be superior to existing liquid decontamination methods for the removal of vapor-deposited cocaine from the surface of hair. Addition of an SFE modifier mixture that contained triethylamine and water allowed the recovery of "matrix-bound" cocaine from hair-binding sites, and extraction efficiencies compared favorably with existing liquid- based extraction procedures. Extraction times in SFE were approximately 30 minutes to 50 minutes, compared with several hours to 1 day for currently used liquid methods. Based on the extraction results observed on drug-fortified and drug-user hair, a displacement SFE mechanism is proposed in which triethylamine competes with cocaine hair-binding sites. The SFE results additionally provide insight into the nature of hair-drug binding interactions and lend support to a current model for drug incorporation in hair. 3 tables, 9 figures, and 30 references