Serotonin receptors of the 5-HT2 type were studied on platelet membranes from 15 patients suffering from major depression. Receptor binding and clinical state (assessed by the Hamilton and Beck rating scales) were examined in a drug free state upon admission and after 1 and 3 weeks of treatment with the antidepressant maprotiline (MPT). 5-HT2 receptor binding changed in correlation with changes in the clinical state of the patients as judged by the rating scales. Since most patients showed a clinical improvement, the patients as a group exhibited a significant decrease in binding concomitant with a drop in depression scores. However, in those patients in whom there was no clinical change or an increase in depression scores, 5-HT2 receptor binding did not change or increased, respectively, thus resulting in a significant correlation between clinical changes and changes in binding. These results support the use of 5-HT2 receptors on platelets in evaluating depression and its treatment.