To separate the independent effects of age and silent myocardial ischemia on the left ventricular response to aerobic exercise, maximal upright cycle ergometry was performed in three groups: 8 clinically healthy older men [76 +/- 3 (SE) yr] with ischemic electrocardiogram (ECG) and Tl scan responses to prior maximal treadmill exercise (old silent ischemic subjects), 16 age-matched men with normal ECG and Tl scan responses (old controls), and 21 healthy young (33 +/- 1 yr) men (young controls). Although the left ventricular ejection fraction, end-diastolic volume index, and end-systolic volume index were similar in the three groups at rest, with increasing work loads there was a progressive increase in the end-diastolic volume index and a blunted decline in end-systolic volume index in the two older groups, which was most apparent in the old silent ischemic subjects. Thus, at peak effort, end-diastolic volume index was largest in old silent ischemic subjects (101 +/- 6 ml/m2), intermediate in old controls (85 +/- 6 ml/m2), and smallest in young controls (67 +/- 3 ml/m2) (P < 0.002); conversely, left ventricular ejection fraction was highest in young controls (85 +/- 2), intermediate in old controls (76 +/- 3), and lowest in the old silent ischemic group (66 +/- 2) (P < 0.001). At exhaustion the peak systolic pressure-end-systolic volume index was significantly lower in the silent ischemic group than in young controls (6 +/- 1 vs. 25 +/- 4 mmHg.ml-1 x m-2, respectively; P < 0.001) with the old controls in between (16 +/- 5 mmHg.ml-1 x m-2).(ABSTRACT TRUNCATED AT 250 WORDS)