It is known both 5-HT2A receptors of platelet and vascular smooth muscle regulate vascular constriction and platelet aggregation to 5-HT challenge. And that 5-HT-induced hypperreactivity of vascular smooth muscle and platelet were noted in patients with coronary artery disease (CAD). In order to investigate the mechanism of platelet hyperreactivity in cardiovascular disease. Platelet 5-HT2A receptor were measured by specific binding of 3H-ketanserin in patients with CAD (CAD group) and patients with chest pain but without CAD as well as healthy subjects (control group) before and after submaximal treadmill exercise. At the same time the levels of plasma 5-HT were also measured. The results showed: (1) In the resting state, 3H-ketanserin exhibited saturable binding with Bmax of 71.1 +/- 10.1 fmol/mg protein, Kd 1.35 +/- 0.20 nmol/L in control group (n = 8) and with Bmax of 102.1 +/- 22.2 fmol/mg protein, Kd 2.44 +/- 0.66 nmol/L in CAD group (n = 10). Between two groups had no significant difference (P > 0.05). And the specific binding of 2.0 nmol/L 3H-ketanserin and the level of plasma 5-HT in CAD group were higher than those in control group (P < 0.05). (2) After exercise all of the specific binding of 2.0 nmol/L 3H-ketanserin, Bmax of receptor binding and the level of plasma 5-HT were significantly increased in CAD group but not in control group. The above results suggested that the up-regulation of platelet 5-HT2A receptor was involved in the platelet hyperreactivity in CAD. The submaximal treadmill exercise had no significant effect on platelet function in control group, but it could lead to platelet 5-HT2A receptor increment and platelet activation in CAD group. Therefore, these changes of platelet might play a role in the acute myocardial ischemia induced by exercise.