OBJECTIVE- To compare the effects of erythromycin and metoclopramide on gastric emptying and symptoms of gastroparesis in diabetic patients with delayed gastric emptying. RESEARCH DESIGN AND METHODS- The study group consisted of 13 patients with symptoms of severe gastroparesis and delayed gastric emptying. Gastric emptying was evaluated using a radionuclide method, and gastrointestinal symptoms were scored. The patients were given either erythromycin (250 mg 3 times/day) or metoclopramide (10 mg 3 times/day) in random order for 3 wk, and after a washout period of 3 wk they were crossed-over to the other medication for another 3 wk. Parameters of gastric emptying were assessed before treatment and after both erythromycin and metoclopramide administration. RESULTS- The half-time of gastric emptying in diabetic subjects was 110 (77-120) min before treatment. At 60 and 90 min, the median value of residual isotope activity was 66.5 (55-83.5) and 55% (43-74.3), respectively. The half-time decreased to 55 min (28.6-115) after 3 wk of treatment with erythromycin and percentages of meal retention in the stomach at 60 and 90 min were 49.9 (38.4-70) and 40.5% (29.7-60), respectively. After taking metoclopramide, the median value of half-time was 67 min (15-115) and percentages of meal retention at 60 and 90 min were 51 (34.5-93.9) and 42% (24-71.2), respectively. When compared with baseline values a significant difference in gastric emptying parameters was found after both erythromycin and metoclopramide. A significant improvement of the total score for gastrointestinal symptoms was observed with both drugs, but this improvement was more pronounced with erythromycin. CONCLUSIONS- Erythromycin, a macrolide antibiotic and a motilin receptor agonist, appears to stimulate intestinal motility and seems to be an alternative agent for the treatment of gastroparesis caused by diabetic autonomic neuropathy.