The effects of erythromycin (EM) on gastrointestinal contractile activity during the interdigestive period were investigated in seven healthy subjects using an infused catheter system, and the changes in the plasma motilin concentration were also determined. Graded EM doses (0.1-1.5 mg/kg) were administered intravenously over 5 min, usually during gastric phase I. EM induced interdigestive migrating contractions (IMCs). Their induction rate was low after low doses of EM, but gradually increased as the dose increased to reach 71.4% at an EM dose of 0.375 mg/kg. Strong contractions, which were quite similar to phase III activity of the stomach but did not migrate or migrated incompletely to the duodenum, were observed at EM doses above 0.375 mg/kg. Therefore, the optimum dose of EM for inducing an IMC was established to be 0.375 mg/kg. In comparison with spontaneous IMCs, EM-induced IMCs had a significantly longer duration in the stomach and a significantly lower amplitude in the duodenum. These observations indicate that EM induced phase III activity more intensively in the stomach than in the duodenum. The plasma motilin concentration increased significantly during EM-induced IMCs, and this suggested a close relationship between this hormone and induction of the IMC. The increase in motilin levels was also observed of the strong gastric contractions which did not migrate or migrated incompletely to the duodenum. Therefore, it seems reasonable to suggest that motilin is involved in phase III activity of the stomach rather than in that of the duodenum.