Based on the results of the in vitro metabolism of CCK8 by various peptidases, we have synthesized three CCK analogs: Boc-Tyr(SO3H)-Nle-Gly-Trp-(N- Me)Nle-Asp-Phe-NH2 (compound I), Boc-Tyr(SO3H)-gNle-mGly-Trp-Nle-Asp-Phe-Nh2 (compound II), Boc-Tyr(SO3H)-gNle-mGly-Trp-(N-Me)Nle-Asp-Phe-NH2 (compound III). In in vitro enzymatic degradation studies, these compounds showed a high stability toward either enkephalinase or the enzymes present in crude rat brain membranes preparations. Moreover, in binding studies on guinea pig tissues, these CCK-related peptides were characterized by high apparent affinities for brain CCK receptors and by a broader range of affinities for pancreatic CCK receptors. This broad range of affinities was reflected by their pharmacological potencies in the guinea pig pancreatic amylase release and ileum contraction assays. These enzyme-resistant CCK analogs provide therefore valuable tools to investigate the pharmacology of CCK.