To evaluate the clinical significance of simple heart rate-adjusted ST segment depression (delta ST/delta HR) in the diagnosis of coronary artery disease, 42 patients with stable exertional angina underwent supine leg exercise testing and cardiac catheterization. During exercise, heart rate, a multilead electrocardiogram, and pulmonary artery wedge pressure were recorded. The sensitivity and accuracy of the delta ST/delta HR criteria (greater than or equal to 3.0 microV/beat/min) were significantly greater than the conventional analysis of ST segment depression criteria (greater than or equal to 0.2 mV) for detecting three-vessel coronary artery disease at a matched specificity of 72% (100% versus 46%, 81% versus 64%, p less than 0.01). A significant linear correlation was found between maximum pulmonary artery wedge pressure increments during exercise (delta PAWP) or Gensini score and the delta ST/delta HR (delta PAWP: r = 0.51, p less than 0.001; Gensini score: r = 0.47, p less than 0.001). There were no statistically significant differences in the delta PAWP or Gensini score between patients with three-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min and those with one- or two-vessel disease who had delta ST/delta HR greater than or equal to 3.0 microV/beat/min (delta PAWP: 18.1 +/- 2.0 versus 21.9 +/- 3.3, p = NS; Gensini score: 68.5 +/- 6.6 versus 66.3 +/- 11.3, p = NS). These findings demonstrate that delta ST/delta HR is more useful than a conventional analysis of ST segment depression for identifying not only anatomically severe coronary artery disease but also functionally severe coronary artery disease.