Delayed gastric emptying occurs in up to 50% of patients after truncal vagotomy and Roux-Y antrectomy and is often resistant to nonsurgical therapy. This study evaluates the effect of erythromycin, metoclopramide, and motilin on delayed gastric emptying in four dogs after Roux-Y antrectomy. Solid food gastric emptying was measured using a radionuclide technique. Study groups were: (1) saline control; (2) erythromycin 1 mg/kg intravenously over 1 hour; (3) erythromycin 3 mg/kg by mouth 45 minutes prior to feeding; (4) metoclopramide 0.6 mg/kg intravenously over 1 hour; and (5) motilin 500 ng/kg intravenously over 1 hour. After Roux-Y antrectomy, saline control dogs had 73% +/- 5% (SEM) gastric retention at 2 hours. After intravenous and oral erythromycin, gastric emptying improved at 2 hours to 27% +/- 6% and 39% +/- 5% (p less than 0.01 compared with control). Erythromycin intravenously and by mouth improved gastric emptying compared with metoclopramide (64% +/- 8%, p less than 0.05). Motilin enhanced gastric emptying to a similar degree as erythromycin, with a 2-hour gastric retention of 37% +/- 4% (NS). Erythromycin improved gastric emptying in dogs with severe Roux-Y gastroparesis and may have clinical application.