Plasma was obtained from 10 human subjects at various intervals after administration of two rapid doses of cocaine, either intravenously or by smoking, and multiple doses by smoking and intravenously. The plasma was analyzed for COC and its metabolites, benzoylecgonine (BE) and ecgonine methyl ester (EME). Plasma concentrations of COC were found to be dose-dependent. For patients receiving two successive doses of COC intravenously (IV) or by smoking (SM), the average half-life of COC was found to be between 38 and 39 minutes, regardless of the dose or route of administration. Considerable interindividual variation was observed. Multiple doses of both SM and IV COC were administered to three patients in a manner consistent with COC abuse. The maximum COC concentration observed was 1.2 mg/L following a total administration of 316 mg of COC over 90 min. Analysis of BE and EME confirmed that BE is the principle metabolite of COC in blood. All COC was accounted for by BE. EME, when present, did not exceed 5% of the BE concentration.