TUMOR necrosis factor-α(TNFα) was infused into the subarachnoid space of the rat rostral basal forebrain, which was previously defined as a prostaglandin (PG) D2-sensitive, sleep-promoting zone. TNFα increased the amount of slow-wave sleep (SWS), decreased that of paradoxical sleep (PS), and caused fever and anorexia. The TNFα-induced SWS enhancement, fever and anorexia were all blocked by co-infusion of diclofenac, a non-selective cyclooxygenase (COX) inhibitor, and by pretreatment with NS-398, a COX-2-specific inhibitor. In striking contrast, the TNFα-induced suppression of PS was not affected by the inhibitors. These results indicate that COX-2-mediated hyperproduction of PGs is critically involved in the enhancement of SWS, fever, and anorexia but not in the suppression of PS, caused by TNFα infused into the PGD2-sensitive zone.