In six healthy persons receiving graded intravenous infusions of synthetic somatostatin the plasma motilin concentrations decreased significantly (p less than 0.05) already with doses giving physiological plasma somatostatin levels, and a rebound of plasma motilin was observed after cessation of infusion of pharmacological somatostatin doses. After an intravenous secretin infusion (280 pmol/kg-h) producing pharmacological plasma secretin concentrations, a comparable plasma somatostatin increase was observed together with a substantial decrease in plasma motilin (p less than 0.05). Infusion of cholecystokinin in a pharmacological dose and of gastric inhibitory polypeptide (GIP) in doses giving plasma GIP levels in the physiological range had no effect on plasma somatostatin or motilin. Circulating plasma somatostatin may be a physiological modulator of the motilin release, and the plasma motilin fall seen during infusion of pharmacological doses of secretin may possibly be explained by the secretin-induced somatostatin release occurring simultaneously.