Background: Seasonal variations in onset of mood disorders and in serotonergic function are reported, but their relationship is unclear. Methods: Circannual variation in platelet 5-HT 2 A binding was measured in 68 healthy subjects and 121 patients with a major depressive episode. In 73 patients the current episode began during Spring or Fall. Results: Significant, but different, circannual variations were found in patients compared with controls. Controls had two peaks of B m a x , one in Spring and another in Fall. Fall and Winter K D was 41% lower compared with Spring and Summer K D . Patients had a peak of B m a x in early Spring and a lesser one in late Fall. B m a x during Spring and Fall was 12% higher compared with Winter and Summer. K D was higher during October through February compared with the rest of the year. B m a x in patients was higher compared with controls in March. The opposite difference was observed in September-December. These differences from controls were mostly due to patients with an onset of the current major depressive episode during Spring or Fall. Conclusions: Patients with a major depressive episode differed from controls in circannual variation of platelet 5-HT 2 A binding. This may reflect a vulnerability to seasonal effects in patients with mood disorders.