The aim of this study was to investigate the effect of a beta-blocker (atenolol and metoprolol) on exercise heart rate (HR) and rate pressure product (RPP) during a morning and afternoon maximal exercise test (maxET) in patients with coronary heart disease (CHD). Twenty-one CHD patients (59.9 ± 8.9 years of age) treated with either atenolol or metoprolol participated in this study. All subjects underwent a morning and afternoon symptom-limited maximal exercise test (maxET) 2–3 h and 8–10 h after medication intake. No significant differences in exercise capacity (atenolol: 8.3 ± 1.9 vs. 8.3 ± 2.1 metabolic equivalents (METs); metoprolol: 8.8 ± 2.0 vs. 8.7 ± 2.0 METs) or rate of perceived exertion (atenolol: 7.4 ± 1.9 vs. 7.4 ± 1.7 METs; metoprolol: 7.2 ± 1.5 vs. 6.8 ± 0.9 METs) were observed between the 2 maxETs in either group. However, there was a discrepancy in cardiovascular and ischemic responses between morning and afternoon maxET. Subjects treated with atenolol demonstrated better overall control of HR and RPP during the afternoon maxET. The difference between morning and afternoon HRmax (11 ± 8 vs. 19 ± 9 beats·min–1; p = 0.05) was significantly higher in the metoprolol group, but did not attain significance for RPP (31 ± 30 vs. 54 ± 28 mmHg·beats·min–1·10−2; p = 0.09). Also, nearly one quarter of our subjects who had a normal morning maxET demonstrated an abnormal electrocardiogram response and (or) ischemia when exercise testing was done in the late afternoon. These changes were more prevalent in subjects taking metoprolol. The results of this study suggest that there is considerable time-of-day variation in the cardiovascular response to a maxET in CHD patients treated with a beta-blocker.