The effects of the calcium antagonist isradipine and the beta-blocker metoprolol, which are based on different antihypertensive therapeutic principles, were evaluated in 52 men with mild-to-moderate hypertension in a 6-week, double-blind, randomized study. Mental stress-testing was performed before and after active treatment. With isradipine (n = 26), the stress-induced responses of cardiac output and total peripheral resistance were not significantly changed, but the blood pressure (BP) response, specifically the diastolic response, was decreased. With metoprolol (n = 26), there was a decreased response of cardiac output and an increased response of total peripheral resistance, and the BP response was even greater than it had been before treatment. Thus, these results indicate that beta-blockade is effective in reducing cardiac responsiveness but, because of vascular counterregulatory mechanisms, BP responsiveness is not decreased. In contrast, calcium antagonism preserves the physiological hemodynamic profile while reducing BP responsiveness to stress.