Total sleep deprivation (TSD) and tricyclic medication are successful treatment modalities for patients with a major depressive disorder. Recent studies have suggested a positive relationship between TSD response and succeeding tricyclic treatment, even on a very specific level, thus supporting the assumption of two distinct biochemical subtypes of depression. The present study tested this hypothesis by treating 10 inpatients with a major depressive disorder first with TSD and succeedingly with clomipramine. Contrary to expectation, a negative relationship between clinical response to the two treatment modalities was found.