Prokinetic agents might be useful in patients with progressive systemic sclerosis (PSS) who have disturbed function of the lower esophageal sphincter and impaired acid-clearance of the tubular esophagus. We therefore compared, by means of esophageal manometry, the effect of 20 mg cisapride orally vs. placebo in 12 patients with progressive systemic sclerosis and proven esophageal dysfunction as well as in 10 healthy volunteers in a double-blind, prospective trial. An increase of the lower esophageal resting pressure from 18.1 +/- 2.4 mm Hg to 23.9 +/- 8.1 mm Hg* after cisapride administration was observed in healthy volunteers, and from 10.9 +/- 3.2 mm Hg to 13.6 +/- 4.0 mm Hg* in the PSS patients. The amplitudes of peristaltic waves in the distal part of the esophagus were increased by cisapride from 83.8 +/- 10.6 mm Hg to 95.6 +/- 15.5 mm Hg* in volunteers and from 28.9 +/- 12.8 mm Hg to 36.8 +/- 16.2 mm Hg in patients (*:P less than 0.05). These results indicate that cisapride has a therapeutic rationale in the treatment of esophageal dysfunction in PSS; further clinical investigations are justified.