Drugs that, directly or indirectly produce activation of serotonin (5-HT) receptors increase plasma concentrations of both prolactin and renin. The serotonergic regulation of prolactin and renin secretion share several common characteristics. Serotonergic neurons originating in the dorsal raphe and terminating in the hypothalamus stimulate the secretion of both prolactin and renin. Destruction of cells in the hypothalamic paraventricular nucleus (PVN) inhibits both the prolactin and renin responses to 5-HT agonists and 5-HT-releasing drugs. Activation of 5-HT2 receptors increases the secretion of both prolactin and renin, while activation of other 5-HT receptor subtypes has differential effects on these hormones. However, there are also differences between the serotonergic mechanisms that regulate the secretion of prolactin and renin. Activation of 5-HT1A receptors increases the secretion of prolactin but not of renin. In addition, activation of peripheral 5-HT2 receptors stimulates the secretion of renin, while activation of peripheral 5-HT3 receptors increases plasma levels of prolactin but not renin. In humans, the effect of 5-HT-releasing drugs and 5-HT agonists on plasma prolactin concentrations has been studied to a greater extent than effects on most other hormones. In contrast, the renin response to 5-HT agonists and 5-HT releasers has not been well characterized in humans. Because of the important role of the renin-angiotensin system in cardiovascular regulation, studies on the serotonergic regulation of renin release in humans could increase our understanding of cardiovascular disorders associated with altered serotonergic function. Examples include anxiety and consequences of cocaine abuse. In conclusion, comparing the serotonergic regulation of prolactin and renin secretion indicates similarities that might shed light on common brain mechanisms that regulate neuroendocrine function.