An electron-capture GLC procedure for determination of plasma ephedrine concentrations is described. The procedure is capable of determining 2 ng/ml of ephedrine and is adequate for following profiles after 25-mg single doses. Pentane extraction of the drug and the internal standard and formation of the N-pentafluorobenzoyl derivatives were followed by GLC. Plasma ephedrine concentrations following a 24-mg dose of ephedrine hydrochloride to a human volunteer are presented. Formation of N-trifluoroacetyl, N-pentafluoropropionyl, N-heptafluorobutryl, and N-pentafluorobenzoyl derivatives and their GLC-mass spectrometric identification are discussed together with comparative electron-capture sensitivities of these derivatives toward a nickel-63 detector. The detection of the N-pentafluorobenzoyl derivative of ephedrine is at least 100-fold greater in sensitivity than detection of the N-trifluoroacetyl derivative.