Erythromycin, a possible motilin agonist, is a potent gastrokinetic agent that may increase the lower esophageal sphincter pressure. Therefore, we assessed the effects of erythromycin in two dosages (250 and 500 mg per os four times a day) on esophageal pH and pressure profiles in reflux patients using prolonged ambulatory monitoring systems. Studies were blinded, placebo-controlled with randomized crossover design. Patients took each drug for three days prior to studies, with erythromycin serum levels obtained the day of esophageal studies. Erythromycin 250 mg four times a day had no effect on esophageal contraction pressures or peristalsis during the day or meal periods. In the supine position, however, erythromycin significantly (P = 0.012) decreased esophageal contraction velocity and showed a strong trend (P = 0.059) towards increasing the percentage of peristaltic waves. Despite these potentially beneficial effects on esophageal clearance, no significant difference in acid exposure times during 24-hr pH studies were observed between placebo and low-dose erythromycin. High-dose erythromycin (500 mg four times a day) was associated with drug levels in the typical antibiotic efficacy range (normal 1-3 micrograms/ml; patients 1.7-7.0 micrograms/ml), but, here again, there was no significant difference in all acid reflux parameters between placebo and erythromycin phases. Therefore, "standard" doses of erythromycin have no important clinical effects on esophageal pressures or acid reflux parameters.