In 24 h water deprived rats we have evaluated the effects of melatonin on the inhibition of thirst and on fever induced by Escherichia coli lipopolysaccharide. Intraperitoneal (i.p) injection of lipopolysaccharide (0.32, 0.64 and 0.96 mg/kg) alone induced, a dose-dependent and significant inhibition of water intake as well as fever. In addition, lipopolysaccharide at the same concentrations increased urinary prostaglandins and serum cytokines levels. On the contrary, lipopolysaccharide treatment had no effects on cerebral brain nitric oxide synthase activity. All lipopolysaccharide effects were reverted by a prior, concomitant and subsequent i.p. treatment with melatonin (2, 4 and 6 mg/kg), whereas they were still present when melatonin was injected in combination with the melatonin receptor antagonist luzindole (15, 30 and 60 mg/kg, i.p.). We suggest that melatonin could exert its dipsogenic effects through a reduction of the free radical nitric oxide (NO.) whereas it may reduce body temperature by preventing an excessive formation of prostaglandins and cytokines.