The antroduodenal motor effects of ranitidine, and H2-receptor antagonist with cholinergic activity, and neostigmine, a cholinomimetic drug, were compared in 16 patients with idiopathic gastroparesis characterized by dysmotility-like dyspepsia, delayed gastric emptying at scintigraphy and absence of gastroduodenal phase 3 of the migrating motor complex during a manometric recording of at least 300 min. After overnight fasting in 8 of these patients, neostigmine was administered intravenously at a dose of 0.5 mg, and in the remaining 8 patients ranitidine was given intravenously at a dose of 100 mg. Ranitidine induced a gastroduodenal phase 3 activity in a significantly (p < 0.02) higher percentage of patients (87.5%) in comparison with neostigmine (25%). In the majority of patients, neostigmine induced only an irregular increase in gastroduodenal motor activity sometimes characterized by propagated and nonpropagated clustered contractions. This property of ranitidine of inducing a phase 3 activity in these patients cannot be ascribed to its weak cholinergic activity, as neostigmine, which has a more intense cholinergic activity than ranitidine, is unable to produce the effect demonstrated by ranitidine. Another unknown mechanism able to trigger the neurohormonal program of migrating motor complex phase 3 or to abolish inhibitory influences should be taken into account to explain this effect of ranitidine.