Effects of stimulation of the splanchnic nerves (gastric sympathetic nerves) on the histamine-induced increases in gastric acid secretion and mucosal blood flow (MBF) were studied in anesthetized rats. The gastric acid secretion and MBF were increased by i.v. infusion of a submaximal dose of histamine (50 micrograms/kg/min). Stimulation of the splanchnic nerve, carried out under an increased steady state of acid secretion and MBF, inhibited the histamine-induced acid secretion and MBF and these effects were abolished by phentolamine and augmented by propranolol. The manner of inhibition by splanchnic nerve stimulation was similar to the inhibitory effects of vasopressin on histamine-induced acid secretion and MBF, but differed from the inhibitory effects of somatostatin; i.v. infusion of vasopressin reduced both histamine-induced acid secretion and MBF, whereas i.v. infusion of somatostatin reduced the histamine-induced acid secretion more effectively than MBF. Inhibitory effects of splanchnic nerve stimulation or infusion of vasopressin on the histamine-induced gastric acid secretion and MBF paralleled the increases in the systemic blood pressure during such treatment. These results suggest that the splanchnic nerves have no direct inhibitory effect on the histamine-induced gastric acid secretion in rats. Decreases in the histamine-induced gastric acid secretion are probably secondary to the decrease in the MBF during splanchnic nerve stimulation.