Increased platelet activity on structurally and functionally impaired endothelium leads to a release of serotonin (5HT), thromboxane A2 and growth factors from platelets. These vasoactive substances may participate in the development of atherosclerosis and thrombovascular events. Platelet aggregatory response to 5HT increases with the height of blood pressure, age, smoking and plasma cholesterol levels. Lipoprotein fractions exert disparate effects an platelets. LDL-cholesterol amplifies 5HT-induced platelet activation whereas HDL-cholesterol inhibits the amplifying effect of LDL-cholesterol. These results indicate that different effects of HDL and LDL-cholesterol on atherosclerotic progression that where found in epidemiological and population studies take place at a cellular level and may represent one of the underlying cellular mechanisms of atherogenesis. This mechanism may be relevant to both atherogenesis and acute thrombovascular events and therefore may represent a target of pharmacological intervention. Effect of calcium antagonists on serotonin- and LDL-induced platelet aggregation were investigated. Isradipin and verapamil (but not diltiazem, amlodipin and felodipin) inhibited at therapeutic concentrations platelet aggregation induced by 5HT in vitro. Isradipin (but not diltiazem and felodipin) also inhibited the amplifing effect of LDL-cholesterol on 5HT-induced platelet aggregation in vitro. Effects of isradipin on 5HT-induced platelet activity as well as on the amplifying effect of LDL-cholesterol were observed also ex vivo. Calcium antagonists differ in their platelet inhibition potency, including their effects on platelet response to 5HT and LDL-cholesterol. These platelet effects of Calcium antagonists appear to be neither group- nor class-specific, but rather drug specific. Effect of isradipin may be relevant to platelet-mediated coronary vasospasm and to prevention of both atherogenesis and thrombogenesis.