Insulin has been shown to increase sympathetic nerve activity (SNA). Although it has been proposed that insulin acts within the central nervous system (CNS) to increase sympathetic neural outflow, there is little evidence for direct central neural sympathoexcitatory effects of insulin. To determine whether intracerebroventricular insulin elicits increases in peripheral SNA, we infused insulin (0.1 microU/min, low; 10 microU/min, medium; and 100 microU/min, high doses) or artificial cerebrospinal fluid (aCSF) into the third cerebral ventricle of chloralose-anesthetized Wistar rats while recording lumbar SNA. In separate animals, 10 microU/min of insulin were infused while recording adrenal SNA and renal SNA. Blood glucose and plasma insulin levels did not significantly change during intracerebroventricular infusion of insulin. Lumbar SNA, expressed as percentage of baseline, did not change in rats infused with aCSF (+ 13% +/- 8%) but increased significantly in rats infused with low (+ 72 +/- 17%), medium (+ 119 +/- 30%), and high (+ 113 +/- 25%) doses of insulin (P < 0.05). Intracerebroventricular insulin failed to significantly increase adrenal SNA or renal SNA. Blood pressure and heart rate did not change during insulin infusion. The results indicate that administration of insulin into the third cerebral ventricle produces regionally nonuniform increases in sympathetic neural outflow in the absence of changes in blood glucose or plasma insulin.