The study provides pharmacokinetic data for exogenous synthetic and endogenous natural motilin in man. Synthetic 13-norleucine-motilin was infused into 6 healthy volunteers at a dose of 0.6 and 2.4 (pmoles per kg) per min over 60 min and plasma motilin was measured by radioimmunoassay. During the infusions mean plasma levels of 124.8 +/- 14.8 and 360 +/- 19.6 pmoles per liter, respectively, were achieved. Disappearance half-time on stopping the infusion was 4.36 min. The apparent volume of distribution was calculated to be 49.4 +/- 3.3 ml per kg, and the metabolic clearance rate was 7.8 +/- 0.5 (ml per kg) per min. To measure the decay of endogenous motilin somatostatin was used in the same 6 subjects. A bolus of 100 mug and a subsequent 15-min infusion of 15 mug per min of somatostatin suppressed the fasting motilin level by 50%. The disappearance half-time was 4.56 min. It is concluded that both synthetic and endogenous motilin are eliminated by first order kinetics with very similar half-times. Our data also suggest that the previously reported motilin infusions at these dose levels gave plasma concentrations within the physiological range and that the effects noted may thus have reflected the physiological actions of motilin.