Cisapride improves reflux esophagitis and enhances esophageal acid clearance. To test the effect of cisapride an salivary production, we enrolled 14 healthy volunteers in a double-blind, randomized, placebo-controlled study. Subjects received cisapride, 10mg per os four times a day, or placebo for three days. Saliva, collected during fasted and fed states, was analyzed for volume and buffer capacity. Buffer capacity was expressed as the volume of 0.01 N HCl needed to titrate 1 ml of saliva to pH 6.1. Both volume and buffer capacity significantly increased during the fed state as compared to the fasted on both cisapride and placebo. Cisapride significantly enhanced the postprandial salivary volume and buffer capacity compared to placebo: 29.6 +/- 11.3 ml vs 22.9 +/- 9.5 ml and 1.07 +/- 0.31 vs 0.89 +/- 0.28, respectively (P< 0.0001). Cisapride's enhancement of salivary flow rate and buffer capacity in the fed state may be another mechanism by which it exerts its beneficial effect in patients with reflux esophagitis.