The effects of diltiazem, a calcium antagonist, on the development of atherosclerosis were studied in Japanese white rabbits. The rabbits were examined at the end of 10 weeks on the following regimens; a diet of standard pellets and daily intraperitoneal (ip) injections of saline; a diet of pellets containing 1% cholesterol and daily ip injections of saline; or a diet of pellets containing 1% cholesterol and daily ip injections of diltiazem (50 mg). The plasma total and LDL cholesterol levels for the third group were significantly lower than those of the cholesterol diet group. Macroscopically, atheromatous lesions covered 26.7% +/- 6.7% (mean +/- SE) of the intimal surface of the aorta in the second group, and 0.7% +/- 0.3% in the third group (p less than 0.005). The levels of cholesterol, calcium, and uronic acid in the aortic tissue of the second group were significantly higher than those in the third. We concluded that diltiazem administered intraperitoneally suppresses the plasma total and LDL cholesterol elevation induced by the cholesterol diet and inhibits experimentally-induced atherosclerosis.