The aim of this study was to determine whether isolated coronary arteries from patients with variant angina show hyperreactivity and/or supersensitivity to acetylcholine in vitro. Coronary arterial rings were obtained at autopsy within 3 h after death from six coronary arteries having spasm in four patients with variant angina and from 22 coronary arteries in 14 control patients with non-cardiac death. The coronary rings were suspended in the organ chamber filled with Krebs Henseleit solution bubbled with 95% O2 + 5% CO2, and their isometric tensions were monitored. Arterial rings isolated from both the patients with variant angina and the controls contracted dose-dependently in response to acetylcholine (10(-9)-10(-5) mol/l). EC50 of acetylcholine (i.e. concentration producing 50% of maximum contraction) was not significantly different between the coronary arteries from patients with variant angina and those from controls, but maximum contraction elicited by acetylcholine (expressed as a percentage of the contraction elicited by 60 mmol/l KCl) was significantly greater in the coronary arteries from patients with variant angina than those from controls. In conclusion, the isolated coronary arteries from patients with variant angina have hypercontractile reactivity to acetylcholine. This intrinsic alteration of the coronary reactivity to acetylcholine may play a role in the genesis of coronary spasm occurring in the situations of enhanced parasympathetic nervous discharge.