Whole blood serotonin (WBS) was measured in 17 patients with DSM-III-R major depression and compared to a healthy control group of 57. Values were significantly lower in the depressed group, but there was no correlation with the degree of depression. Four patients with a history of suicide attempts had even lower levels, but this was not statistically significant. Across all subjects, there was an effect of season of sampling, with values in spring significantly higher than those in autumn. Since blood serotonin is primarily produced peripherally, these results suggest that some aspect of peripheral serotonin metabolism is abnormal in major depression.