Cigarette smoking has been causally linked to coronary heart disease. To investigate the effect of smoking on the activity of ischemic heart disease, 65 patients with chronic stable manifestations of coronary disease and a positive exercise tolerance test underwent continuous ambulatory monitoring to quantify the amount of ischemic ST segment depression during daily life. Twenty-four smokers were compared with 41 nonsmokers for frequency and duration of electrocardiographic signs of ischemia during 24 hours. A total of 4,968 hours of ambulatory monitoring were analyzed. The frequency of episodes was three times as often (median) and the duration of ischemia was 12 times longer (median duration, 24 vs 2 min/24 h) in smokers than nonsmokers. This finding remained statistically significant when a number of potentially confounding factors were controlled by means of logistic regression. This study shows that patients with coronary artery disease who smoke have significantly and substantially more active myocardial ischemia during daily life than patients who do not.