The uptake of [14C]5-HT, [3H]paroxetine and [3H]LSD binding was determined in platelets from 30 untreated patients with major depression and compared with corresponding variables from 30 healthy age-, sex- and season-matched control subjects. The maximum velocity (Vmax) for the 5-HT uptake was significantly decreased in patients (P = 0.014) compared to control subjects. Depressed women had significantly lower Vmax than female control subjects. In men, Vmax did not differ between patients and control subjects. Vmax was significantly lower in male inpatients compared with male outpatients (P = 0.05). The density (Bmax) of 5-HT uptake sites was found to be significantly increased in patients (P < 0.05) compared to control subjects and male patients had significantly higher Bmax than male control subjects, but there was no difference between female control subjects and female patients. No significant difference was found in Bmax of 5-HT2-receptors between patients and control subjects. A positive correlation was found between Bmax of 5-HT2-uptake sites and the degree of anxiety and between Bmax of 5-HT2 receptors and MADRS scores. Bmax of 5-HT2-receptors was positively correlated with the degree of suicidality. The results in the present study indicate that there may be a gender difference in serotonergic dysfunction in depression.