The luteinizing hormone (LH) response to metoclopramide (MCP), a dopamine receptor antagonist, and naloxone (NAL), an opioid receptor antagonist, was evaluated in 7 patients with polycystic ovarian disease (PCOD) before and during treatment with purified human urinary follicle-stimulating hormone (hFSH), and in 6 control women during spontaneously ovulating cycles. Before treatment, in all patients both MCP and NAL administration did not increase plasma LH levels. In the 6 subjects ovulating following hFSH treatment the LH response to MCP and NAL at preovulatory and midluteal phases was restored, as it occurred in control women. Our results suggest that in PCOD the dopamine and opioid activity in the hypothalamus are decreased. The reversal of peripheral ovarian response induced by treatment for the induction of ovulation may restore these impaired neuroendocrine activities.