Effects of vagotomy, acetylcholine and various adrenergic drugs on serum immunoreactive gastrin levels were studied in the rat. In rats fasted 24 h or longer serum gastrin concentrations generally were < 50 pg/ml; 60 min after onset of feeding, serum gastrin concentrations reached levels > 100 pg/ml. In rats fasted overnight, injections of epinephrine, isoproterenol and phenoxybenzamine all raised the serum gastrin level. Pretreatment with propranolol, a .beta.-adrenergic blocking agent, abolished the hypergastrinemic affect of isoproterenol. Administration of propranolol lowered basal serum gastrin levels and reduced the increase in serum gastrin produced by feeding. In vagotomized rats, isoproterenol futher increased already elevated serum gastrin levels, while propranolol alone slightly reduced elevated basal gastrin levels in 4 or 5 vagotomized rats. Bathing the antral mucosa by gavage with isoproterenol (even in 0.01 N HCl) increased serum gastrin levels, indicating that isoproterenol acted directly on the antrum and not indirectly by elevating intragastric pH. Possible interactions between cholinergic and adrenergic agents on serum gastrin responses were examined. Acetylcholine given by gavage produced its well known large increase in serum gastrin. An anticholinergic drug, atropine, given orally, greatly restricted ability of acetylcholine to raise serum gastrin, and propranolol given orally inhibited increase in serum gastrin levels produced by oral acetylcholine. The idea is supported that cholinergic and adrenergic systems influence gastrin secretion in the rat.