The inhibition of parotid secretion by pentagastrin increased with dose for jugular and carotid injections (0.01-0.16 micrograms/kg) in acute preparations of 3 sheep anesthetized with sodium pentobarbital. The intracarotid effect exceeded that for the jugular both in magnitude across all doses and in slope relating % inhibition to ln dose (p less than 0.005). The greater depression from carotid injections indicated that the effect was mediated in the head in response to higher pentagastrin concentrations at any dose level. In other experiments, both secretion and associated efferent activity in the parotid nerve were depressed more by carotid than jugular injections of pentagastrin, secretion being reduced by 27.2 vs. 12.1% and efferent activity by 43.2 vs. 20.6% respectively (p less than 0.025). These results indicate that gastrin in the circulation may be able to inhibit parotid secretion in sheep by acting directly on the central nervous system.