A specific, sensitive, rapid and reproducible analytical method for zimelidine [3-(4-bromophenyl)-N,N-dimethyl-3(3-pyridyl)allylamine] and its biologically active demethylated metabolite, norzimelidine, in human plasma was developed using gas-liquid chromatography (GLC) with loxapine as the internal standard. A good separation of zimelidine and norzimelidine was obtained following derivatisation of norzimelidine with heptafluorobutyric anhydride, the retention times being 6.16 and 10.35 minutes, respectively. The sensitivity of the method is 5 ng/ml for zimelidine and norzimelidine.Plasma concentrations of zimelidine and norzimelidine were determined in 10 healthy volunteers following the administration of a single oral dose of 100mg zimelidine. Zimelidine was rapidly absorbed, giving a mean peak plasma concentration of 103.9 ± 34.8 ng/ml. The mean plasma elimination half-life was 8.4 ± 2.0 hours for zimelidine and 19.4 ± 3.6 hours for norzimelidine. After long term administration of zimelidine (100mg bid for the first week, 100mg tid for the second week and 100mg am and 200mg pm for the third and fourth weeks) to 2 depressed patients, plasma concentrations of norzimelidine were 2 to 4 times higher than those of zimelidine.