The action of acetylcholine (ACh) on extramural coronary arteries (CA) of dogs, pigs, and humans was tested in vitro. ACh dilated precontracted canine CA in dependence on the state of endothelium. This dilation was mediated through muscarinic receptors since atropine inhibited it effectively. Preparations without active precontraction were not influenced at all or slightly dilated. Both human and porcine CA were exclusively contracted by ACh independently of the presence or absence of precontraction. The ACh contraction in porcine CA was found to be endothelium-independent, but also inhibited by atropine as well as the ACh contraction in human CA. Adrenoceptor blockers did not influence ACh reactivity. High concentrations of ACh (greater than 10(-5) mol/l) decreased the further responsiveness of the vessels to the mediator (tested in dogs and pigs only). Spontaneous mechanical activity was registered only in human CA. Different ACh reactivity in dogs compared with pigs and humans is interpreted as species-dependent. It must be taken into account when human coronary physiology is modeled in animals.