The effects of naltrexone methobromide, a quaternary derivative of the opioid antagonist naltrexone, were investigated on deprivation (24 h)-induced water intake in the unilaterally cannulated rats. Naltrexone methobromide reduced post-deprivational water intake with an ED50 of 7.3 micrograms when tested at 30 min (peak effect) after intracerebroventricular administration. It also dose-dependently (0.3-10 micrograms) depressed water intake, with peak effects at 15 min, after microinjection into the paraventricular hypothalamic nucleus and into the supraoptic hypothalamic nucleus. The drug did not produce any other effects on behaviors. The ED50S were 1.4 micrograms when given into the paraventricular nucleus, and 3.3 micrograms when given into the supraoptic nucleus, respectively. Although injections of higher doses (1.0, 3.0 and/or 10 micrograms) of the drug into the preoptic area, zona incerta, and corpus callosum significantly suppressed water intake, other behavioral manifestations, such as rotational behaviors, convulsions, body shakes, head swaying, and/or backward locomotion were manifested simultaneously with the reduction in drinking. When injected into the lateral hypothalamic area, water intake was not significantly affected by the drug. These findings suggest that the paraventricular and supraoptic hypothalamic nuclei are important sites of action in the naltrexone-induced suppression of water intake.