The aim of this study was to determine the optimal dosage regimen of cisapride for the treatment of idiopathic gastroparesis. We studied 17 patients with documented idiopathic gastroparesis in a three-way, cross-over, double-blind study with three 4-day treatment periods separated by at least 3 days without treatment. In each period, the patients were preloaded with cisapride (10 mg tid) for three days. On the fourth day (the test day) they took either 10 mg or 20 mg before breakfast and placebo before lunch (1 x 10 mg), (1 x 20 mg), or 10 mg before breakfast and 10 mg before lunch (2 x 10 mg). The medications were taken 30 min before meals. Gastric emptying of solids (99mTc-sulphur colloid) was measured at lunch time under basal conditions and during each treatment period. Plasma concentrations of cisapride were determined before the breakfast dose, before the lunch dose, and at 1, 2, 3, 4 and 5 h after. The greatest acceleration in gastric emptying occurred with the 2 x 10 mg regimen. Although the single morning dose of 20 mg also significantly accelerated gastric emptying (P = 0.05), the reduction was not as substantial. Plasma concentrations of cisapride were significantly higher after 2 x 10 mg than after 1 x 20 mg or 1 x 10 mg. There was a significant relation between cisapride plasma concentrations and changes in gastric emptying. Peak concentrations of cisapride greater than 60 ng.ml-1 were invariably associated with acceleration of gastric emptying. We conclude that cisapride 10 mg tid before meals is the optimal dose for the treatment of idiopathic gastroparesis.