We tested the effects of nifedipine, a calcium antagonist, on atherogenesis in rabbits fed a 2% cholesterol diet. The drug was given orally, 40 mg/dl, and control rabbits received placebo. Nifedipine was well tolerated, and evoked only transient, moderate reductions in arterial pressure. Plasma total cholesterol after 8 wk before killing the rabbits was similar in the placebo and nifedipine-treated groups, averaging 1,903 +/- 138 (n = 13) and 1,848 +/- 121 mg/dl (n = 13; mean +/- SE; P greater than 0.8). In placebo-treated rabbits, aortic lesions stainable with Sudan IV covered 40 +/- 5% of the intimal surface, and the cholesterol concentration in aortic tissue was 47 +/- 5 mg/g protein. Corresponding values for the aortas from nifedipine-treated rabbits were significantly lower and averaged 17 +/- 3% (P less than 0.001) and 29 +/- 2 mg/g protein (P less than 0.001). We conclude that nifedipine suppressed atherogenesis without reducing hypercholesterolemia.