The clinical significance of monitoring the plasma levels of amitriptyline and its metabolites in prediction of the clinical outcome of depressive episode was investigated in 49 inpatients. Discriminant analysis of drug concentrations (at two weeks after initiation of drug treatment) and clinical outcome revealed that increasing the plasma levels of amitriptyline, cis-isomers of hydroxylated metabolites (Z-10-hydroxyamitriptyline and Z-10-hydroxynortriptyline) predicted a better clinical outcome, while increasing of plasma levels of nortriptyline and trans-isomers of hydroxylated metabolites (E-10-hydroxyamitriptyline and E-10-hydroxynortriptyline) were shown to predict a poor clinical outcome in the depressive episode of the subjects, and that clinical outcome of approximately 73% of the subjects could be correctly predicted.