Metapramine (Timaxel) and his three major metabolites (19148 RP, 23669 RP, 19749 RP) have been determined in the plasma of 18 depressed inpatients treated by the antidepressant drug (12 women and 6 men; 7 are smokers and 11 non-smokers). In a steady state, interindividual variability is very important, especially for 23669 RP. No significant correlation exists between normalized doses (mg.kg-1) and normalized plasma concentrations (ng.ml-1/dose mg.kg-1) of metapramine or anyone of its metabolites. The plasma metabolic ratios reveal also important intraindividual and interindividual variability. Two populations of patients seem to exist: extensive metabolizers and relatively poor metabolizers, without apparent clinical consequence because 23669 RP shows an antidepressant activity. Women seem, with equal normalized doses, to exhibit higher plasma levels of unchanged metapramine than men, due to a lower protein-binding rather than to a more active metabolism. In patients who received a poly-medication smoking seems not to induce desmethylation of metapramine. The plasma metabolic ratios, compared by the analysis of variance and the Wilcoxon distribution-free test, are significatively influenced by sex and not by tobacco-smoking.