Previous studies show that the radionuclide-derived indices of left ventricular (LV) diastolic performance are abnormal at rest in many patients with coronary artery disease (CAD), even in those with normal resting ejection fraction (EF) and no prior myocardial infarction. This study examined the age-related changes in LV peak filling rate and time to peak filling rate in 65 subjects between the ages of 20 and 75 years with a low likelihood of CAD. All subjects had normal resting EF (greater than or equal to 50%), and none had prior infarction. There was a significant age-related decline in resting peak filling rate (r = -0.47, p less than 0.001) and exercise peak filling rate (r = -0.52, p less than 0.001), but no age-related effect in the time to peak filling rate. Of the 29 subjects less than 50 years of age, 26 (90%) had resting peak filling rate greater than or equal to 2.5 EDV/sec (3.1 +/- 0.6, mean +/- SD) compared to 17 of 36 subjects (47%) greater than or equal to 50 years of age (2.6 +/- 0.6) (p = 0.002). In a subgroup of 28 subjects with a history of hypertension, the age-related effect was more marked than in the remaining 37 subjects without such a history (r = -0.66 vs -0.33). Thus, the peak filling rate at rest and during exercise decreases with advancing age; the high frequency of observed abnormality in the peak filling rate at rest in patients with CAD may conceivably be related in part to age differences between patients with CAD and the control group.