The hyperventilation (HV) test has been extensively used in different forms of coronary artery disease. The purpose of this work was to investigate the response to HV in patients with syndrome X and compare HV with exercise (EX) test. The authors studied 20 patients with syndrome X (angina, a positive EX test, and normal coronary angiogram) and 20 healthy subjects who underwent HV and EX tests. In 7 patients, all women, angina and electrocardiographic (ECG) changes occurred during HV but in none of the controls. Patients with syndrome X and controls had a similar rate-pressure product (RPP) at rest and achieved a similar RPP with HV. The RPP achieved with HV in patients with syndrome X without ECG changes was significantly lower, 121.8 +/-29.1(mean +/-SD), than what was achieved by those with changes, 167.9 +/-42.9, P < 0.01. In patients with an abnormal response to HV the RPP at which angina and ECG changes occurred was similar to that where similar changes were observed during EX. There was a significant correlation of the RPPs between the two tests, r=0.82, P < 0.02. In contrast, in patients in whom no angina or ECG changes occurred, the RPP they achieved with HV was significantly lower than the anginal threshold during EX 204 +/- 47.4, P < 0.0001. In conclusion, a significant proportion of patients with syndrome X, mainly women, who achieve a high RPP with HV, develop angina and ECG changes during overbreathing. The close relation between EX and HV RPPs where these changes occur suggests an increased myocardial oxygen demand as the most likely underlying mechanism for this behavior.