1. We investigated the vagal pathways mediating the gastric accommodation reflex in the rat stomach. 2. Gastric distension (6 ml) evoked an increase of 9.0 +/- 1.0 cmH2O of intragastric pressure in vivo. Pretreatment with tetrodotoxin (TTX) caused a significant pressure increase by gastric distension, reaching 17.0 +/- 1.7 cmH2O, suggesting mediation by neural pathways. 3. The pressure increase evoked by gastric distension was significantly enhanced in vivo by acute truncal vagotomy (TV), hexamethonium (C6), and NG-nitro-L-arginine methyl ester (L-NAME), but not by vasoactive intestinal polypeptide (VIP) antiserum, guanethidine, or splanchnicotomy. 4. Gastric distension (6 ml) evoked a much larger intragastric pressure in the denervated, vascularly isolated, perfused rat stomach in vitro. Intra-arterial application of TTX and L-NAME did not cause further pressure increases evoked by gastric distension. 5. The pressure increase evoked by gastric distension remained high 2 weeks after TV in vivo. However, the accommodation reflex was fully restored 4 weeks after TV in vivo. This reflex was antagonized by TTX, C6 and L-NAME, but not by VIP antiserum, guanethidine and splanchnicotomy. 6. Similar to in vivo studies, gastric distension caused a smaller increase in intragastric pressure in response to gastric distension in the denervated, vascularly isolated, perfused stomach obtained from rats 4 weeks after vagotomies in vitro. The pressure increase evoked by gastric distension was significantly enhanced by L-NAME, hexamethonium and TTX. 7. It is suggested that the vago-vagal reflex plays an important role in mediating the accommodation reflex. This involves a vagal efferent pathway that uses nitric oxide as a final neurotransmitter mediating gastric relaxation in intact rats. It is also suggested that the adaptive mechanism mediating the accommodation reflex following vagotomy occurs in the gastric myenteric plexus.