Summary:Eight patients are described who displayed excessive concentrations of nortriptyline, imipramine, or clomipramine on routine blood level monitoring. Under these conditions, the patients did not respond to the treatment. All patients were markedly improved when the daily dosage of the antidepressant was reduced with a simultaneous decrease of the blood concentrations. Among these eight patients, seven suffered from side‐effects, three were characterized as poor hydroxylators of debrisoquine, while three had concomitant treatment with a phenothiazine.