The vagus has a dual effect on gastrin: it both stimulates and inhibits its release. To determine the gastric vagal pathways for these opposing effects, plasma gastrin and acid responses to meal (intragastric titration of 15% liver extract, pH 5.5) and to insulin (0.5 U regular insulin intravenously) were studied in seven dogs in three consecutive stages: a control stage, after antral vagotomy (AV), and after subsequent proximal gastric vagotomy (PGV). AV abolished the plasma gastrin response to insulin but had no effect on either basal or meal-stimulated gastrin release. Subsequent PGV caused significant elevation in basal plasma gastrin concentration, no further change in the gastrin response to insulin, but a significant increase in meal-stimulated gastrin release. AV decreased acid response to insulin nonsignificantly and had no effect on meal-stimulated acid secretion. Subsequent PGV reduced by 90% the acid response to insulin, had negligible effect on the gastric fistula acid response to meal, but increased Heidenhain pouch response sixfold. These studies show that vagal stimulation of gastrin release is mediated along direct antral vagal pathways, while vagal inhibition requires intact vagal fibers to the proximal stomach. The mechanism by which the fundic vagal pathways exert an inhibitory influence on the G cell in the antrum is yet to be elucidated.