The relationship between ischemic ST depression and oxygen uptake kinetics was examined during cardiopulmonary exercise test using the ramp protocol in 22 patients (17 males and 5 females, mean age 61.4 +/- 8.1 years) with ischemic ST change (horizontal or down sloping ST depression over 1 mm) during a previous multi-stage exercise test (Bruce method). Patients were classified into three groups according to coronary angiographic findings: absence of significant stenosis group (control, n = 7), single-vessel disease group (n = 7) and multivessel disease (MVD) group (n = 8). Peak exercise time, peak heart rate, peak systolic blood pressure, anaerobic threshold, peak oxygen uptake (peak Vo2), exercise time, heart rate, systolic blood pressure, and oxygen uptake at appearance of ischemic ST change were measured. The ratio of oxygen uptake increase at appearance of ischemic ST change was calculated. Peak Vo2 was lower in the MVD group than in the control group (20.9 +/- 6.2 vs 27.3 +/- 3.3 ml/min/kg, p < 0.05), and exercise time from the beginning of ramp exercise to the appearance of ischemic ST depression was shorter in the MVD group than in the control group (5.2 +/- 2.1 vs 8.2 +/- 1.9 ml/min/kg, p < 0.05). The ratio of oxygen uptake increase was smaller in the MVD group than in the control group (0.7 +/- 0.3 vs 1.2 +/- 0.2, p < 0.01). These results could be caused by impaired increase of cardiac output due to myocardial ischemia occurring during exercise. In the clinical setting, these phenomena could be used as a parameter for differentiating ischemic from non-ischemic ST depression or evaluating the sensitivity of ischemic heart disease.