The gastrointestinal motor effects of the macrolide antibiotic, azithromycin, were compared with those of midecamycin acetate. The method of investigation consisted of intraluminal pressure measurements in the gastric antrum and upper small intestine by means of a low compliance perfused catheter system. Eleven healthy volunteers participated in the single blind, placebo-controlled study of both interdigestive and postprandial gastrointestinal motility. Azithromycin was administered by mouth in a single 500 mg dose or in two daily doses of 250 mg; midecamycin acetate was given in a dose of 600 mg b.i.d. The effect of midecamycin acetate on gastric antral and jejunal motility was not significantly different from that of placebo. This was true for both the interdigestive and the postprandial phases of gastrointestinal motility. Peroral treatment with azithromycin resulted in a statistically significant increase in the postprandial antral motility index as compared to placebo. This increase was observed in the distal antrum as well as in the proximal antrum. In addition, the gastric contractions were found to originate higher up in the stomach after azithromycin as compared to placebo or midecamycin acetate.