This study was designed to investigate the participation of cholecystokinin(CCK)-A and/or CCK-B/gastrin receptors in CCK-8-induced contraction of guinea pig caecal circular smooth muscle cells, using a novel selective CCK-A receptor antagonist, (S)-N-[1-(2-fluorophenyl)-3,4,6,7-tetrahydro-4-oxo-pyrrolo-[3,2,1-jk][1,4]be nzodiazepine-3-yl]-1H-indole-2-carboxamide (FK480), and a novel selective CCK-B/gastrin receptor antagonist, (R)-1-[2,3-dihydro-1-(2 -methylphenacyl)-2-oxo-5-phenyl-1H-1,4-benzodiazepi ne-3-yl]-3-(3-methylphenyl)urea (YM022). Concentration-response curves for the contractile effect of CCK-8 alone and in the presence of 0.1nM FK480, 0.1nM YM022, or a combination of 0.1nM FK480 and 0.1nM YM022 on isolated smooth muscle cells were determined. In addition, the inhibitory effects of various concentrations of FK480 or YM022 on 1nM CCK-8-induced contraction were examined. At a concentration of 0.1nM, both FK480 and YM022 shifted the concentration-response curve for CCK-8 to the right (about 100 times) with the same potency. In addition, a concentration-response curve for a combination of 0.1nM FK480 and 0.1nM YM022 was shifted to the right (about 100 times) of the curves for 0.1nM FK480 alone or 0.1nM YM022 alone. Both antagonists inhibited 1nM CCK-8-induced contraction of caecal circular smooth muscle cells in a concentration-dependent manner, with the similar inhibitory potency. A significant inhibition was obtained at a concentration as low as 0.1nM FK480 and 0.1nM YM022. This study strongly suggested the presence of both CCK-A and CCK-B/gastrin receptors in caecal circular smooth muscle cells of guinea pig, and that the contractile effect of CCK-8 on these cells was mediated via both of these receptors.