Tricyclic antidepressants have been used frequently as pharmacological probes in neuroendocrine studies even though they appear to lack neurochemical specificity. Despite this, the hormonal responses to these drugs have been used to provide evidence that depressed patients have alterations in both noradrenergic and serotonergic tone within the central nervous system. Most studies have been conducted in the morning, which is not a time of high physiological neuroendocrine secretory activity. The present study has used the relatively specific serotonergic probe intravenous clomipramine given to depressed patients and healthy subjects immediately before sleep onset, which is a time of increased neuroendocrine activity. Under these conditions, 12.5 mg clomipramine stimulates the secretion of both cortisol and prolactin, but unlike studies conducted in the morning, clomipramine suppresses the secretion of growth hormone in both groups. These data suggest that serotonergic mechanisms are involved in the regulation of the secretion of these three hormones at the time of sleep onset.