Cholesterol-fed rabbits were used to test potential anti-atherosclerotic effects of diltiazem, a calcium antagonist of the benzothiazepine type. Two groups of 7 rabbits each were fed standard laboratory chow supplemented with 1% cholesterol. One group received a 60 mg sustained release diltiazem capsule twice a day and the other group received a placebo capsule twice a day. A third group of control animals were fed an unmodified basal diet under conditions exactly the same as the experimental groups. All groups were studied over a period of 16 weeks. The cholesterol-fed animals showed a marked increase in plasma total cholesterol which was not significantly different for the diltiazem and placebo groups. Plasma calcium levels, blood pressure, and heart rate were also unchanged from the control animals. In the diltiazem-treated animals, 47.5 +/- 10.5% of the aortae showed atherosclerotic lesions; the value for the placebo group was 43.1 +/- 8.1%. Similar results were obtained for the coronary arteries. These results show that diltiazem treatment in the doses employed in this study had no effect on the reduction of atherosclerosis in this animal model.