108 male rabbits, aged 6 months, with experimental hypercholesterolemia and experimental abdominal aortic lesioning received different regimen of antiatherosclerotic treatment; 36 of them were treated with isradipine, a dihydropyridine calcium antagonist (0.3 mg/kg/daily), 36 with isradipine in combination with aspirin whereas 36 animals received placebo. The entry of 125I-radiolabelled LDL into the aorta was demonstrated to be significantly diminished in isradipine-treated rabbits as well as positive Sudan-III-staining and aortic cholesterol content were in comparison to placebo. This benefit was almost completely abolished by concomitant aspirin-treatment. The notable increase in vascular prostacyclin (PGI2) is supposed to mediate the strong antiatherosclerotic effect of isradipine resulting in an inhibition of LDL-entry and vascular cholesterol accumulation. Aspirin almost totally blocked the raise in PGI2-synthesis by the inhibition of cyclooxygenase detected in isradipine-treated animals. It can be concluded, that aspirin-treatment may minimize the antiatherosclerotic actions of calcium antagonists which are mediated by the PG-system.