We aimed to evaluate the gastric relaxant capacity of the 5-HT_1/7 receptor agonist 5- carboxamidotryptamine (5-CT) in conscious dogs and to clarify the mechanism of action by use of selective antagonists, vagotomy and in vitro experiments. A barostat enabled us to monitor the intragastric volume in response to different treatments (intravenously administered) before and after supradiaphragmatic vagotomy [results presented as the maximum volume change after treatment (mean; n=5-11)]. In vitro experiments were performed with isolated muscle strips cut from 4 different stomach regions of the vagotomized dogs [results were fitted to the operational model of agonism to determine the efficacy parameter (n=5)]. 5-CT (0.5-10 µgkg^-1) caused a dose-dependent gastric relaxation (29-267 ml), that was completely blocked by the selective 5-HT₇ receptor antagonist SB-269970 (50 µgkg^-1). After vagotomy, the relaxation to 10 µgkg^-1 5-CT was significantly less pronounced (73 vs. 267ml; P<0.05) but still blocked by SB-269970 while the response to the NO-donor nitroprusside was similar to that before vagotomy (178 vs. 218ml). In vitro, 5-CT concentration-dependently inhibited the PGF₂- contracted muscle strips before and after vagotomy. Although before and after vagotomy the response in every region was mediated by 5-HT₇ receptors (pA₂ SB-269970: 8.2-8.6 vs. 8.3-8.6 respectively), the response after vagotomy was less efficacious (log : 1.9 to 0.5 vs. 1.4 to -0.1 respectively). The results indicate that the 5-CT-induced proximal stomach relaxation in conscious dogs before and after vagotomy is mediated via 5-HT₇ receptors. The decreased efficacy of 5-CT in vitro after vagotomy is probably related to vagotomy-induced changes in receptor density or coupling-efficiency and provides a possible explanation for the decreased in vivo response to 5-CT after vagotomy.