The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, on spontaneous and interleukin-1 (IL-1)-induced sleep were examined in rabbits. Animals were injected intracerebroventricularly or intravenously during the light phase with vehicle, L-NAME, IL-1, or the combination of L-NAME and IL-1. Injection of L-NAME (5 mg icv and 100 mg/kg iv) suppressed both non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) for 4-6 h. The sleep-suppressive effects are unlikely due to pressor responses to L-NAME because administration of L-NAME (5 mg icv) produced only a transient (3-4 min) slight increase in systemic blood pressure. Injection of IL-1 (20 ng icv) elicited fever, suppressed REMS, and increased NREMS for 6 h. NREMS was suppressed for 3 h after the combined intracerebroventricular injections of 5 mg L-NAME and 20 ng IL-1 and was elevated during postinjection hours 4-6. Administration of IL-1 (30 ng/kg iv) increased NREMS and brain temperature for 2 h. After the combined injection of IL-1 and L-NAME (100 mg/kg), NREMS was significantly suppressed during postinjection hours 1-5. It is not known whether the interactions
 between the sleep-suppressive effects of L-NAME and the NREMS-promoting effects of IL-1 are specific, being mediated via a common mechanism, or whether they are additive, being mediated via independent mechanisms. The pyrogenic and REMS-suppressive actions of either intracerebroventricularly or intravenously injected IL-1 were not affected by L-NAME.