1. We have tested whether 5-HT3 receptors mediate vagally-induced relaxation or contraction of the isolated stomach of the guinea-pig. 2. The antagonists of 5-HT3 receptors, ondansetron (1-10 microM) or metoclopramide (1-30 microM) did not inhibit vagally-induced relaxations at low concentrations but partially inhibited them at 30 microM or 60 microM, respectively. These higher concentrations of ondansetron and metoclopramide also inhibited relaxations induced by 1,1-dimethyl-4-phenylpiperazinium iodide (30 microM) but did not affect those induced by glyceryl trinitrate (0.7-1.1 microM). 3. Desensitization to 5-HT (100 microM) or 2-Me-5-HT (100 microM) did not affect relaxations or contractions induced by vagal stimulation. 4. Ondansetron (30 microM) or metoclopramide (60 microM) did not inhibit vagally-induced gastric contraction. 5. Thus, 5-HT3 receptors do not mediate vagally-induced relaxation or contraction in the guinea-pig stomach.