There is evidence that blood platelets accumulate, store and release 5-hydroxytryptamine (5-HT, serotonin) in a manner analagous to the central nervous system serotonergic synaptosome. The biogenic amine hypothsis of affective disorders states that depression is associated with a deficiency of brain 5-HT. Therefore, a study was carried out to compare the platelet 5-HT uptake characteristics of platelets from depressive patients and healthy control subjects. The rate of platelet 5-HT uptake was lower in depressive patients than in age and sex matched control subjects. There was no correlation between severity of illness and rate of 5-HT uptake, and the results for a group of patients tested both when depressed and again after recovery were similar on the two occasions. It is suggested that a low rate of 5-HT uptake is a trait contributing to a predisposition to depressive illness. A seasonal variation in 5-HT transport was observed in both controls and patients. The rate of 5-HT uptake was lowest in late spring and early summer, which is also the time of year of greatest incidence of depression and the peak in the suicide rate. Inhibition of 5-HT uptake was observed in depressed patients treated with either amitriptyline or zimelidine. The extent of inhibition of 5-HT transport was related to plasma drug concentrations, but did not correlate with clinical improvement. Prophylactic treatment with lithium increased the rate of platelet 5-HT uptake towards normal values in both unipolar and bipolar patients. The significance of these findings and their possible relationship to some other biochemical abnormalities observed in depressive patiente are discussed.