In order to assess the possible role of the new candidate gut hormone, motilin, in controlling the interdigestive migrating motor complex (MMC) in man, 14 normal subjects were studied after an overnight fast by means of three pressure-recording catheters with orifices 25 cm apart in the upper small intestine. The typical aboral progressing bursts of pressure waves occurred at a mean interval of 137 minutes and were preceded by a peak motilin level 25 pmol/liter higher than the lowest level in the postactivity-front quiescent period. To study the effect of exogenous motilin, an infusion of pure porcine motilin at various dose levels was given to 16 normal volunteers shortly after the onset of the phase I quiescent period. Motilin infusion induced an activity front in 12 of the 16 subjects. The mean activity front interval was reduced to 46 min (P less than 0.001). This effect could be obtained even at the low dose level of 0.4 pmol/kg/min, which produced an increase in plasma motilin level of only 57 pmol/liter. These data suggest that a cyclic rise in plasma motilin levels is one of the factors involved in the production of the activity front of the migrating motor complex in man.