Somatostatin (SST) has been shown to induce cholestasis in the dog and in the rat. In man, it is still unknown whether SST modifies bile formation. The present study was undertaken to examine the influence of SST on bile secretion in man. Two volunteers who had a total external biliary fistula received 1-hour SST infusions (3.5 micrograms/kg/h). Bile flow, bile acid, phospholipid and cholesterol biliary outputs were measured before, during and 1 h after the infusion. The SST infusion was associated with a pronounced decrease in bile flow and in bile acid secretion and with an increase in bile cholesterol saturation. These findings suggest that SST has cholestatic properties in man as in other species. This may provide a rational explanation for the formation of gallstones and for the steatorrhea observed in patients with somatostatinomas or during therapeutic SST administration.