The study was carried out to determine the relationship between ventilatory threshold and the onset of ischaemia, as shown on the ECG (horizontal and/or descending ST depression of 0.05 mV, on average). Twenty-seven male patients (aged 58+/-7 years) with angiographically documented coronary artery disease (CAD) were assessed by cai cardiopulmonary exercise testing without medication. Oxygen uptake (VO2), heart rate (HR), rate-pressure-product (RPP) and blood lactate were measured and/or calculated every 30 s during exercise. In addition, IO patients, comparable with the above group, were examined to find out the acute effects of isosorbide dinitrate (ISDN) at ventilatory threshold in relation to ischaemic threshold. The first cardiopulmonary exercise test was carried out without medication, the second 1 h later, with 5 mg ISDN, taken sublingually 30 min before the test. Results: (($) over bar x, SD). The mean ventilatory threshold preceded the ischaemic threshold in I elation to exercise capacity (48+/-14 vs 55+/-20 watts: P<0.05), VO2.kg(-1) (10.0+/-2.2 vs 12.0+/-2.9 ml.kg(-1).min; P<0.05), HR (93+/-15 vs 100+/-16.min(-1); P<0.01), RPP (15095+/-4424 vs 17166+/-5245; P<0.01) and blood lactate (1.28+/-0.53 vs 1.44+/-0/60 mmol.l(-1); P<0 05). (2) This relationship was observed mole often in the subgroup of patients with angina during cardiopulmonary exercise testing ol with myocardial infarction or with three-vessel disease than in patients without angina or infarction or with one- and two-vessel disease. (3) ISDN improved the ischaemic threshold from 55+/-26 watts (without medication) to 81+/-32 watts (P<0.01) but not the ventilatory threshold (56+/-23 vs 59+/-21 watts, ns). Conclusion: The ventilatory threshold seems to precede the ischaemic threshold because of impaired aerobic capacity of the leg muscles, caused by deconditioning on account of the disease. However, ischaemia-induced left ventricular dysfunction did not seem to have a direct influence on ventilatory threshold as ISDN improved the ischaemic threshold, but not the ventilatory threshold.