Intracellular calcium concentrations ([Ca++]i) in blood platelets from 11 depressed patients and 11 healthy controls were investigated. The resting [Ca++]i of platelets from depressed patients was 69.4 +/- 2.9 nM while that from controls was 74.6 +/- 4.0 nM. Serotonin (5-HT), at a concentration of 10 microM, increased [Ca++]i by 129.2 +/- 3.9 nM in platelets from depressed patients, which was significantly greater than that found in platelets from control subjects (105.2 +/- 6.0 nM). Norepinephrine (NE) 100 microM increased [Ca++]i by 46.1 +/- 7.1 nM in platelets from depressed patients, and by 38.6 +/- 6.1 nM in platelets from controls, respectively. These results indicate that 5-HT2 receptor function in platelets of depressed patients is enhanced, and support the hypothesis of hypersensitivity of 5-HT2 receptors in affective disorders.