Dopamine is postulated as an inhibitory neurotransmitter in the alimentary tract. The purposes of this study were to determine the effect of levodopa on the rate of gastric emptying in man and to investigate the interaction of levodopa and metoclopramide (a putative dopamine antagonist) on gastric emptying. On separate days, 7 normal male subjects received oral levodopa, 1,000 mg, and placebo in a randomized double-blind fashion 20 min before taking a mixed solid-liquid test meal labeled with 99mtechnetium(Tc)-diethylenetriamine pentaacetic acid. Gastric emptying was measured over 90 min by a gamma camera technique. At 90 min, the mean percent isotope remaining in the stomach after placebo, 54.7 +/- 5.0%, was less than after levodopa, 85.1 +/- 4.9% (p less than 0.01). Four of these normal subjects were studied further, and received levodopa, 1,000 mg, and metoclopramide, 10 mg, by intramuscular injection, 20 min before the same labeled test meal. In these 4 subjects, at 90 min, mean percent isotope remaining in the stomach after the combination of levodopa and metoclopramide, 48.5 +/- 2.2%, was less than after levodopa alone, 83.3 +/- 7.0% (p less than 0.05), and in the same range as mean percent after placebo, 47.3 +/- 3.6%. It is concluded that (1) levodopa inhibited gastric emptying of isotope in a mixed solid-liquid meal in normal subjects; (2) metoclopramide antagonized this effect returning gastric emptying to normal; and (3) the data suggest the possibility that dopaminergic receptors have an inhibitory effect on gastric emptying of the human stomach.