Calcium antagonists inhibit atherogenesis in the cholesterol-fed rabbit without producing hypolipidaemia, suggesting a direct action on the arterial wall. In this study, the effects of several calcium antagonists on the myoproliferative response to balloon catheter injury of the aorta have been investigated in normolipidaemic rats and rabbits. The incorporation of [3H]thymidine into rat aortic DNA 48 h after balloon injury was markedly reduced by twice daily oral administration of nifedipine, verapamil, diltiazem or lanthanum. DNA synthesis in other proliferating tissues was unaffected. Twice daily oral administration of prazosin or minoxidil, antihypertensive agents that are not calcium antagonists, also selectively reduced arterial DNA synthesis. In balloon catheterised rabbits twice daily oral administration of nifedipine (10 mg/kg) caused a 39% reduction in the cross-sectional area of the neo-intima 14 days after injury. These results show that nifedipine and other antihypertensive agents inhibit smooth muscle cell proliferation.