A high performance-liquid chromatographic procedure employing electrochemical detection (LCEC) was developed for the quantitation of a new narcotic antagonist, a nalmefene, in human plasma. Following extraction of the plasma at pH 9, the extract was chromatographed on a reverse-phase C18 column using naltrexone as an internal standard. An electrochemical detector equipped with a glassy carbon electrode monitored the elution of nalmefene and the internal standard. The method had a limit of sensitivity of 3 ng/ml of nalmefene using a 1 ml sample of plasma and the calibration curve was linear over a range of 3-200 ng/ml. The intra- and inter-assay coefficients of variation did not exceed 6 and 12%, respectively, over the entire range of the calibration curve. The LCEC method was used to quantitate the plasma concentrations of nalmefene in man following oral administration of 64 mg of the drug. In 1 subject, a peak plasma concentration of 58 ng/ml occurred 2 h after drug administration and declined to 5 ng/ml after 24 h.