Vasospastic angina was observed in two sisters. The 52-year-old younger sister presented with rest angina at midnight and in the early morning. The coronary arteriogram showed no significant organic stenosis. Vasospasm to the left anterior descending and right coronary arteries was induced by the intracoronary administration of acetylcholine. The 57-year-old elder sister complained of rest and effort angina. Her coronary arteriogram was also normal. Vasospasm to the left circumflex and right coronary arteries was provoked by acetylcholine. In both cases, human leukocyte antigen DQw3 was negative. In the present cases, genetic factors may partly contribute to the mechanism of vasospastic angina.