The effect of three doses of erythromycin on interdigestive gastrointestinal motility and on plasma motilin levels was studied in healthy volunteers and patients with diabetic gastroparesis. Abnormalities of interdigestive motility were observed in 40% of the patients. In healthy volunteers, 40 mg erythromycin elicited a premature phase 3 that started in the stomach. In contrast to the spontaneous gastric phase 3, this erythromycin-induced phase 3 was not accompanied by a motilin peak. In patients with diabetic gastroparesis, 40 mg erythromycin induced a premature phase 3 in three patients, no response in one patient, and a burst of antral contractions in another patient. Doses of 200 and 350 mg erythromycin elicited a burst of antral phase-3-like contractions in both volunteers and patients, which was not accompanied by a motilin peak. This phase-3-like activity did not migrate to the small intestine and was not followed by a phase 1, but by a prolonged period of antral contractile activity. The number and amplitude of antral contractions after 200 or 350 mg erythromycin were significantly higher than after 40 mg. The motor patterns induced by different doses of erythromycin offer potential therapeutic applications.