Escherichia coli LPS (640-1280 mcg/Kg, intravenously) showed a powerful, dose-dependent and long-lasting inhibitory effect on drinking behavior stimulated by 48 h water deprivation, subcutaneous injection of isoprenaline (33.3 mcg/Kg) and intracerebroventricular injection of hypertonic NaCl (2.9%) solution, carbachol (250 ng) and angiotensin II (100 ng). The antidipsogenic effect was neither a consequence of behavioral alterations, nor due to endotoxin peripheral vasodilating activity. Naloxone (60-120-240 mcg/Kg, subcutaneously) did not influence endotoxin inhibition of water intake, thus ruling out an endorphin-mediated effect. When prostaglandin synthesis was inhibited, the effect of endotoxin was reduced. Since prostaglandins do not seem to be involved in the regulation of thirst, the mechanism of the antidipsogenic effect elicited by endotoxin needs further study.