Serotonin (5-HT) uptake in blood platelets from depressed patients and normal controls were studied over a 2-year period to determine if seasonal variations were present. Vmax, a measure of the number of 5-HT uptake sites in normal controls and depressed patients, was significantly higher in fall and winter than in spring and summer; Vmax in the depressed patients was lower than in normal controls throughout the year. Normal controls showed lower Vmax in April and June. A similar trend was present in the depressed patients but the lowest values were found in the month of December. The necessity of considering seasonal variations in this and other putative biological markers is emphasized.