Fifteen healthy subjects, fasted at least 8 hr, were studied by means of an infused manometric method. Twenty minutes after termination of the natural phase III activity in the duodenum, erythromycin or normal saline was administered intravenously for 15 min. When normal saline (N = 5) was infused, the next migrating motor complex (MMC) was initiated 151.2 +/- 42.1 min after the infusion. On the other hand, when erythromycin was infused at a rate of 1.0 mg/kg/hr (N = 5) or 3.0 mg/kg/hr (N = 5), MMC-like contractions were initiated at shorter intervals, ie, 47.8 +/- 40.9 min (P less than 0.005) or 23.0 +/- 13.0 min (P less than 0.001) respectively. The duration, frequency, amplitude, and migrating velocity of the naturally occurring MMC (N-MMC) were not significantly different from those of the erythromycin-induced contractions except for the duration of the phase III contractions in the stomach; the duration (5.3 +/- 2.2 min) of the erythromycin-induced contractions being significantly (P less than 0.05) longer than that (3.2 +/- 0.9 min) of the naturally occurring MMC. The immunoreactive motilin (IRM) concentration did not increase significantly after the infusion of erythromycin, when compared to that after infusion of normal saline. It is concluded that erythromycin at a dose of 1-3 mg/kg/hr for 15 min during the interdigestive state, similar to motilin, has a significant influence upon the initiation of MMC in the human gastrointestinal tract, but further investigations are required to confirm whether endogenous motilin is involved or not.