Older age, the cardiovascular risk factors and arteriosclerosis have been reported to be associated with stimulated platelet function. To evaluate the relative importance of these factors in determining platelet function, a cross-sectional multivariate study in 191 men, 113 healthy subjects and 78 patients with angiographically documented coronary heart disease, was performed. In healthy subjects, stepwise multiple linear regression identified age to be a major determinant of platelet aggregability. After induction with both ADP and collagen the platelet aggregatory response markedly increased with age. In the patients, platelet function was not age dependent. In multivariate analysis of variance, neither smoking status nor hypercholesterolemia (greater than or equal to 240 mg/dl) were determinants of platelet function in either group. An increase in systolic blood pressure was associated with slightly more inhibited ADP induced aggregation in both healthy subjects and patients with coronary heart disease. In patients compared to healthy subjects, aggregation after induction with ADP and collagen was markedly enhanced and the in vitro formation of thromboxane after collagen stimulation increased. Thus, by multivariate analysis, age and the presence or absence of coronary heart disease were found to be major determinants of platelet function. In contrast, the cardiovascular risk factors smoking, hypercholesterolemia and hypertension were associated with only minor or no alterations of platelet function.