OBJECTIVES: The purpose of this study was to determine the antihypertensive agent(s) more likely to mitigate an exaggerated rise in exercise blood pressure (BP) in hypertensive patients. BACKGROUND: An exaggerated rise in exercise BP is associated with increased cardiovascular risk. There are no recommendations for treating such response. METHODS: Participants were hypertensive men (n = 2,318; age 60 +/- 10 years), undergoing a routine exercise test at the Veterans Affairs Medical Center, Washington, DC. Antihypertensive therapy included angiotensin-converting enzyme inhibitors (n = 437), calcium-channel blockers (n = 223), diuretics (n = 226), and combinations (n = 1,442), beta-blockers alone (n = 201) or in combination with other antihypertensive agents (n = 467), and none (n = 208). Exercise BP, heart rate (HR) and rate-pressure product (RPP) at maximal and submaximal workloads were assessed. RESULTS: After adjusting for covariates, patients treated with beta-blockers or beta-blocker-based therapy had significantly lower BP, HR, and RPP at 5 and 7 metabolic equivalents (METs) and peak exercise than those treated with any other antihypertensive agent or combination (p < 0.05). The likelihood of achieving an exercise systolic BP of >/=210 mm Hg was 68% lower (odds ratio = 0.32, 96% confidence interval 0.2 to 0.53) in the beta-blocker-based therapy versus other medications. African Americans exhibited higher BP and HR than Caucasians at all exercise workloads regardless of antihypertensive therapy and had over a 90% higher likelihood for an abnormal exercise BP response. This risk was attenuated by 35% with a beta-blocker-based therapy. CONCLUSIONS: Significantly lower exercise BP, HR, and RPP levels are achieved with beta-blocker-based therapy than with other antihypertensive agents regardless of race. However, BP was better controlled in Caucasians than in African Americans regardless of antihypertensive therapy.