The relationship between somatostatin and the interdigestive migrating motility complex (MMC) was determined in human volunteers. Motor activity was monitored manometrically by means of seven perfused catheters: four in the stomach, one in the duodenum, two in the jejunum. Blood samples were drawn every 10 min and radioimmunoassayed for motilin, pancreatic polypeptide and somatostatin. In four volunteers two activity fronts (AF) were recorded and somatostatin levels correlated to the manometric data. The start of an AF in the upper duodenum was accompanied by somatostatin peaks. Peak values, taken as the mean of the levels in the sample obtained after the start of an AF, the preceding sample and the next one, averaged 32 +/- 4 pM compared to 12 +/- 2 pM in the remaining period. In four volunteers somatostatin was infused in doses of 1.2, 2.4 and 4.8 pM/kg per min over three consecutive periods of 90 min, causing dose-dependent increments in plasma somatostatin levels of 7, 32 and 76 pM. In all volunteers and for all doses all gastric activity was completely inhibited. In the intestine phase 2 was abolished but phase 3 stimulated: during somatostatin infusion phase 3 occurred with an interval of 39 +/- 6 min. Motilin and PP levels were decreased. As the two lowest infusion doses caused increases in somatostatin levels that might be considered as physiological, somatostatin seems to have a physiological role in the regulation of the migrating motor complex. We propose that it facilitates the progressing of the activity front into the small intestine.