Only bipolar lead recording are available during ambulatory monitoring. Their sensitivity in detecting ST segment changes in relation to standard electrocardiographic leads is not known. The magnitude and direction of ST segment changes in the bipolar lead CM5 were compared with those in standard electrocardiographic leads in patients during exercise testing and percutaneous transluminal coronary angioplasty. Thirty patients with coronary artery disease were studied during exercise tests in which ST segment depression (greater than 0.5 mm) occurred in one or more standard electrocardiographic leads and 13 patients were studied during angioplasty that resulted in ST segment change in one or more leads (I, II, III, V2, V5, and CM5). Lead CM5 was the most sensitive lead (93%) during exercise testing and also showed the greatest magnitude of ST segment change below the isoelectric line in 93% of the patients. Only two patients, one with ST segment elevation in inferior leads and one with changes restricted to septal leads, had no ST segment depression in lead CM5. When ST segment shift from the baseline electrocardiogram was measured the magnitude of depression was greatest in lead CM5 in only 63% of the patients. During angioplasty of the left anterior descending coronary artery, lead CM5 showed ST segment depression in seven patients, ST segment elevation in two, and a biphasic response in one. Two of the three patients with balloon inflation in right coronary artery developed ST segment elevation in lead CM5. Thus lead CM5 is a reliable lead for detecting subendocardial ischaemia experienced during everyday activities in anginal patients. During total occlusion of coronary arteries (as in variant angina or myocardial infarction) lead CM5 commonly shows ST segment depression and changes due to right coronary artery occlusion may not be detected.