The possibility of vagal reinnervation to intrasplenic islet grafts was examined by measuring portal insulin response to electric stimulation of the dorsal vagus nerve in autografted dogs. Grafted islets responded appropriately to an exogenous cholinergic agent given intravenously. However, no insulin secretory response could be observed in grafted dogs after vagal stimulation, which markedly increased portal insulin levels in control dogs. Therefore, intrasplenic islets are not under direct vagal control. At the basal state, normal oscillatory release of insulin was observed in the animals with grafts, suggesting that the mechanism of rhythmic basal insulin release is intrinsic to the islet of Langerhans with no regulatory input from the vagus nerve or any element of pancreatic structure.