The colonic motor response to eating requires cholinergic transmission. Recent studies have identified two subclasses of muscarinic receptor, the M1 and the M2 subtype. The aim of this study was to evaluate the muscarinic receptor subtype responsible for mediating the gastrocolonic response. Spike potential (SP) activity and intraluminal pressure were recorded, during fasting and after eating a 1000-kcal mixed meal, from the distal colon of 10 healthy volunteers. In each subject three paired studies were carried out: either atropine (a nonselective antimuscarinic, 1 mg), pirenzepine (a selective M1 antimuscarinic, 10 mg), or saline were infused intravenously before eating, using a double-blind crossover design. The meal significantly increased colonic spike potential activity (17.6 +/- 3.9, SP/30 min) above fasting values (2.7 +/- 0.6, P less than 0.01) in the control study. There was no postprandial increase in spike potential activity (3.3 +/- 0.9, SP/30 min) after atropine. The meal also significantly increased spike potential activity (15.4 +/- 3.3 SP/30 min, P less than 0.01) above fasting levels and equal to that of the controls, in the pirenzepine study. These data suggest that the colonic motor response to eating is mediated through the M2 but not the M1 subtype of muscarinic receptors.