Interstitial cells of Cajal (ICC) are proposed to play a role in stretch activation of nerves and are under investigation for potential roles in enteric innervation. Most data to support such roles comes from in vitro studies with muscle strips while data at the whole organ level are scarce. To obtain insight into the role of ICC in distention- induced motor patterns developing at the organ level, we studied distension-induced adaptive relaxation in the isolated whole stomach of wild-type and W/W^v mice. Pressure development was monitored throughout infusion of 1 ml solution over a 10 min period. The final intraluminal pressure was sensitive to blockade of nitric oxide synthase, in wild-type and W/W^v mice to a similar extent, indicating NO mediated relaxation in W/W^v mice. Adaptive relaxation occurred between 0.2 and 0.5 ml solution infusion; this reflex was abolished by TTX, was not sensitive to blockade of nitric oxide synthase but was abolished by apamin, suggesting that ATP and not nitric oxide is the neurotransmitter responsible for this intrinsic reflex. Despite the absence of intramuscular ICC (ICC-IM), normal gastric adaptive relaxation occurred in the W/W^v stomach, however, ICC-IM may play a role in development of myogenic tone. In conclusion, a mouse model was developed to assess the intrinsic component of gastric accommodation. This showed that ICC-IM are not essential for activation of intrinsic sensory nerves nor ATP driven adaptive relaxation nor NO mediated relaxation in the present model. ICC-IM may be involved in regulation of myogenic tone.