We studied the effect of erythromycin on gastric emptying in nine patients with gastroparesis following truncal vagotomy and antrectomy, and assessed their clinical response to chronic oral erythromycin. Gastric emptying was evaluated using a solid-phase radio-labeled meal. Patients were studied after erythromycin 200 mg intravenously (N = 9) and after an oral suspension of erythromycin 200 mg (N = 7) each given 15 min after ingestion of the meal. Three parameters of gastric emptying were analyzed: half-emptying time (T1/2), area under the curve, and percent gastric residual at 2 hr. Nine patients were subsequently placed on oral suspension erythromycin 150 mg three times a day before meals (range 125-250 mg three times a day) and symptoms of nausea, vomiting, postprandial fullness, and abdominal pain were assessed before and after erythromycin. Intravenous erythromycin markedly accelerated the gastric emptying (all three parameters studied) of solids (P < 0.01) in seven of nine patients with postsurgical gastroparesis [baseline T1/2 154 +/- 15 min; after intravenous erythromycin, T1/2 56 +/- 17 min (mean +/- SEM)]. Oral erythromycin enhanced (P < 0.05) the gastric emptying rate (T1/2, area under the curve) in five of seven patients (baseline T1/2 146 +/- 16 min; after oral erythromycin, T1/2 87 +/- 20 min). Of the nine patients who were placed on oral maintenance erythromycin, three showed clinical improvement after two weeks. In summary, erythromycin significantly enhances gastric emptying in many patients with vagotomy and antrectomy-induced gastroparesis; however, only a small subset of patients respond clinically to chronic oral erythromycin.