Tritiated imipramine binding in platelets has been used to evaluate serotonin activity in depression in previous studies. This article examined this marker as a possible measure of central nervous system serotonergic activity for depression in patients with Parkinson's disease (PD). The number of binding sites was significantly lower in depressed patients with PD than in a healthy control group. Patients with PD who were not depressed had lower values than the comparison group, but this difference was not significant. We also found a significant correlation between the receptor site values in platelets and cerebrospinal fluid levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (r = .59), but this was independent of a diagnosis of depression. Receptor site values were examined to identify appropriate cutoff scores to predict depression in the group of patients with PD. A maximum sensitivity of 50% was achieved with a specificity of 64%. Our results strongly support a generalized alteration in serotonin metabolism in depressed patients with PD, but tritiated imipramine binding in platelets is not a useful diagnostic tool for depression.