Somatostatin is known to inhibit the postprandial release of most gastrointestinal hormones. The aim of the present study was to evaluate the effect of an analog of somatostatin, SMS 201-995 (120 ng/kg/hr), on both meal-induced and cholecystokinin octapeptide (CCK-8, 500 ng/kg/hr)-induced peptide YY (PYY) release. Six mongrel dogs with distal ileal Thiry-Vella loops were used in this study. PYY was measured in both plasma and ileal luminal effluent. SMS 201-995 did not affect interdigestive plasma or ileal luminal PYY concentrations. CCK-8 and a fat meal both stimulated PYY release into the circulation. SMS 201-995 completely inhibited the CCK-8 and fat-stimulated circulatory release of PYY. Both CCK-8 and a mixed meal increased ileal luminal PYY recovery. SMS 201-995 inhibited CCK-8-induced, but not meal-induced, ileal luminal PYY recovery. These findings support previous studies that describe independent circulatory and ileal luminal PYY release. We conclude that both somatostatin and CCK may have a regulatory role in postprandial circulatory release of PYY.