Piribedil, a compound that stimulates dopamine receptors in a relatively specific fashion, was administered to 11 hospitalized depressed patients. The dopamine agonist significantly decreased rapid eye movement (REM) sleep and percent REM sleep and increased REM latency. Piribedil decreased the probenecid-induced accumulation of the dopamine metabolite homovanillic acid (HVA) in CSF. A range of mild to moderate antidepressant effects was noted; one patient worsened and one developed recurrent manic episodes. The degree of improvement in depression was negatively correlated with pretreatment values of HVA in CSF (r = -.66, P less than .05). These data suggest that the heterogeneity of clinical response may be related to biological differences in depressed patients and that those with low initial dopaminergic function respond best to increased dopamine receptor stimulation.