Platelet uptake of 5-hydroxytryptamine (5-HT) and dopamine (DA) in normal subjects in vitro has already been shown to be significantly inhibited by clomipramine and less markedly by maprotiline (Turner and Ehsanullah, 1977). This effect has now been studied in greater detail, in patients categorized as having endogenous or neurotic/reactive depression, treated or untreated, and in normal volunteers, in whom the inhibitory activity of the metabolite desmethylclomipramine was also studied. Platelet uptake of 5-HT and DA in both types of depression is lower than in healthy, which supports the hypothesis that central monamine function is reduced or impaired in depressives. Clomipramine potently inhibits platelet uptake of DA as well as 5-HT, its antidepressant action cannot be attributed to 5-HT alone, while the observation that maprotiline has no effect on 5-HT uptake shows that its antidepressant action is not based on a serotonergic mechanism. Desmethylclomipramine has a marked inhibitory effect on platelet 5-HT uptake and its effect on DA uptake is greater than that of the parent compound.