The effect of the putative enteric neurotransmitters neurokinin A and substance P were investigated on human small intestinal motility. Either neurokinin A, at doses of 6-25 pmol/kg/min, or substance P at doses of 1-6 pmol/kg/min were administered intravenously to healthy volunteers over 4 hr. Neurokinin A dose-dependently increased the fraction of phase II of the migrating motor complex, contraction frequency, motility index, and amplitude of contractions. At the highest dose, neurokinin A induced a phase II-like pattern, disrupting the migrating myoelectric complex. Substance P dose-dependently increased phase II of the migrating motor complex. The contraction frequency increased slightly at the highest dose, but neither motility index nor contraction amplitude changed. It is concluded that neurokinin A and substance P stimulate small intestinal motility in man, and it can be speculated that they play a role in the control of human small intestinal motility.