There is growing interest in the use of alternate biological fluids for drug testing. An advantage of oral fluids is that collection can be made from individuals under direct observation without undue embarrassment or invasion of privacy. This study evaluated the STC Cocaine Metabolite MICRO-PLATE EIA for use in detection of cocaine and metabolites in oral fluids. Intra- and interassay precision of the EIA was < 10%. The EIA was cross-reactive to benzoylecgonine (100%), cocaine (> 12.9%), and cocaethylene (13.8%), but did not demonstrate detectable cross-reactivity with other commonly encountered medicants. Evaluation of a series of potential adulterants of oral fluids indicated that common household chemicals and foodstuffs did not alter the outcome of EIA testing for cocaine metabolite. Analysis by EIA and by gas chromatography-mass spectrometry (GC-MS) of oral fluids and urine specimens collected from current drug users in treatment programs and subjects participating in research studies involving controlled dosing of cocaine provided assessment of the clinical sensitivity and specificity of the STC Cocaine Metabolite EIA. Analysis of the data by means of receiver operating characteristic (ROC) plot indicated that the optimal cutoff concentration for the oral fluids EIA was 10 ng/mL. In comparison to GC-MS (10-ng/mL combined cutoff concentration for cocaine and benzoyleogonine), the EIA (10-ng/mL cutoff concentration) demonstrated a sensitivity, specificity, and accuracy of 95%, 82%, and 88%, respectively. The oral fluids EIA was slightly less sensitive than the urine EIA (300-ng/mL cutoff concentration) for the detection of cocaine metabolite with a sensitivity, specificity, and accuracy of 73%, 85%, and 88%, respectively. Overall, testing of oral fluids for cocaine metabolite with the STC Cocaine Metabolite MICRO-PLATE EIA appears to offer a viable alternative to urine for detection of recent cocaine use.