Propionate (0, 1, 2, 4, 8, 16, 32, and 64 mumol.kg BW-1 x min-1 for 30 min) was infused i.v. to investigate the physiological effects of propionate on insulin and glucagon responses in sheep. An i.v. propionate infusion (32 mumol.kg BW-1 x min-1 for 30 min) with adrenergic and cholinergic blockades was also conducted to clarify the role of autonomic innervation in the control of propionate-induced insulin and glucagon responses. In the experiment in which we studied responses to propionate infusion, the concentrations of plasma insulin and glucagon during propionate infusion increased (P < .05) from the preinfusion concentrations at infusion rates of > 4 and 8 mumol.kg BW-1 x min-1, respectively. The incremental response areas of plasma insulin and glucagon during propionate infusion increased (P < .05) at infusion rates of > 16 and 32 mumol.kg BW-1 x min-1, respectively. In the experiment studying the effects of adrenergic and cholinergic blockades on responses to propionate, the insulin incremental response area during propionate infusion was suppressed (P < .05) by atropine infusion but it was not influenced by phentolamine, propranolol, or hexamethonium infusions. The glucagon response area was suppressed (P < .05) by phentolamine infusion, but it was not influenced by propranolol, atropine, or hexamethonium infusions. It is concluded that in sheep 1) propionate may have a physiological role in stimulating insulin and glucagon responses, 2) the propionate-induced insulin response is partly due to the parasympathetic nervous system through activation of a muscarinic receptor, and 3) the propionate-induced glucagon response is stimulated by adrenergic alpha-receptors.