An ideal drug regimen for physically active hypertensive patients should not offset exercise-induced improvements in cardiovascular health or fitness. In this randomized, double-blind, placebo-controlled, crossover study of 39 physically active men with uncomplicated essential hypertension, we compared the effects of atenolol and enalapril on cardiovascular fitness and serum lipids. Drugs (atenolol, 50 or 100 mg once daily; enalapril, 10 or 20 mg once daily) were each administered for 4 weeks and each active drug period was preceded by 4 weeks of placebo therapy. Both drugs effectively (p < 0.001) lowered resting blood pressure when measured at the time of theoretical peak (i.e., 3 to 4 hours postdrug) and trough (i.e., 24 hours postdrug) drug blood levels. Atenolol reduced maximal oxygen uptake (by 7.3%, p < 0.001) 3 to 4, but not 24, hours after drug ingestion; no changes occurred with enalapril. Similarly, whereas serum lipids were essentially unchanged with enalapril, serum triglycerides (18.9% increase), high-density lipoprotein cholesterol (10.6% decrease), and ratio of low-density to high-density lipoprotein cholesterol (15.4% increase) were adversely impacted (p < or = 0.05) with atenolol. It is concluded that in contrast to enalapril, atenolol adversely impacts cardiovascular fitness and serum lipids and lipoproteins in physically active hypertensive men.