Catheterization of the portal vein and stereotaxic implantation of electrodes in the ventrolateral hypothalamus (VLH) were performed in normal rats after thiopental anesthesia. Immunoreactive glucagon (IRG), insulin (IRI), And glucose were monitored in portal plasma before and during electrical stimulation of the VLH (6 micro A, 50 Hz, 2 msec each, for 15 min). This stimulation induced a significant and reproducible IRG rise, followed by hyperglycemia. IRI remained unchanged. These alterations were not observed in control rats, i.e. in the absence of implantation; after VLH implantation without stimulation; or after implantation in the hippocampus or in the nucleus lenticularis. Bilateral splanchnicectomy abolished the IRG rise and hyperglycemia which followed VLH stimulation, while IRI was elevated both before and during electrical stimulation. Bilateral vagotomy did not suppress the A cell response to VLH stimulation, and it significantly reduced the IRI concentration in both basal and stimulatory periods. This resulted in sustained hyperglycemia. Attempts at total denervation of the pancreas induced patterns similar to that observed after splanchnicectomy alone. These results suggest that stimulation of the VLH can influence the endocrine pancreas and blood glucose levels by sympathetic nervous inputs which stimulate A cells and inhibit B cells.