Intravenous injection of Escherichia coli endotoxin (LPS; 640 micrograms/kg) produced an antidipsogenic effect in 48-h water-deprived rats, which was antagonized by acetylsalicylic acid (ASA; 0.45, 0.9 microM) injected directly into cerebral preoptic area (POA). ASA (0.9 microM) when injected into POA did not elicit, by itself, any effect on drinking. Endotoxin (0.5, 1, and 2 micrograms), when injected directly into POA, produced a dose-dependent inhibition of drinking stimulated by water deprivation. This effect was antagonized by ASA (0.45 microM) injected into POA 15 min before LPS. Injection of LPS (2 micrograms) into brain areas not involved in drinking regulation (superior colliculus or nucleus caudatus) was without effect on 48-h water deprivation-induced thirst. PGI2 (5, 50, and 500 ng) injected ino POA showed a dose-dependent antidipsogenic effect on drinking stimulated by water deprivation. The data suggest that prostaglandins, within the preoptic area, might be involved in the antidipsogenic effect of E coli LPS, given either intravenously or directly into POA.