Impaired left ventricular (LV) diastolic filling at rest is frequently observed in patients with coronary artery disease (CAD) who have normal LV systolic function and no previous infarction. To test the hypothesis that abnormal diastolic function at rest might reflect the functional severity of CAD, as estimated by exercise-induced ischemia, the relation between regional and global LV diastolic function at rest and during exercise-induced ischemia was evaluated in 49 patients with radionuclide angiography. All patients had normal systolic function at rest. Group 1 (n = 26) patients manifested a normal ejection fraction response to exercise and group 2 (n = 23) patients an abnormal response. Data obtained from 22 age-comparable normal volunteers were used for comparison. Although regional and global diastolic function were not different between normal subjects and group 1 patients, peak filling rate was lower in group 2 patients than in normal subjects (2.5 +/- 0.8 vs 3.2 +/- 0.6 end-diastolic counts/s; p less than 0.01). Moreover, regional diastolic asynchrony, as assessed from the radionuclide data by using a regional sector analysis of the LV region of interest, was greater in group 2 patients (46 +/- 44 ms) than in both normal subjects (25 +/- 16 ms; p less than 0.05) and group 1 patients (23 +/- 16 ms; p less than 0.05). Thus, among patients with CAD and with normal LV systolic function at rest, impaired LV filling and regional asynchrony predict a greater degree of exercise-induced ischemia, suggesting a greater extent of jeopardized myocardium.