We investigated the contributions of forebrain, brain stem, and spinal neural circuits to interleukin (IL)-1-induced sympathetic nerve discharge (SND) responses in -chloralose-anesthetized rats. Lumbar and splenic SND responses were determined in spinal cord-transected (first cervical vertebra, C1), midbrain-transected (superior colliculus), and sham-transected rats before and for 60 min after intravenous IL-1 (285 ng/kg). The observations made were the following: 1) lumbar and splenic SND were significantly increased after IL-1 in sham C1-transected rats but were unchanged after IL-1 in C1-transected rats; 2) intrathecal administration of DL-homocysteic acid (10 ng) increased SND in C1-transected rats; 3) lumbar and splenic SND were significantly increased after IL-1 in sham- but not midbrain-transected rats; and 4) midbrain transection did not alter the pattern of lumbar and splenic SND, demonstrating the integrity of brain stem sympathetic neural circuits after decerebration. These results demonstrate that an intact forebrain is required for mediating lumbar and splenic sympathoexcitatory responses to intravenous IL-1, thereby providing new information about the organization of neural circuits responsible for mediating sympathetic-immune interactions.