Paraoxonase-1 (PON1) can protect endothelial function by preventing the oxidation of low-density lipoprotein (LDL) cholesterol and retarding the development of atherosclerosis. We examined whether PON1 polymorphism influences endothelium-dependent coronary vasomotor responses. Sixty-seven patients underwent diagnostic cardiac catheterization, but showed no significant coronary artery stenosis. In all patients, PON1 genotypes (Q/Q, Q/R and R/R) were determined, and provocative testing was performed by the intracoronary administration of graded doses of bradykinin (BK; 0.2, 0.6 and 2.0 mug/min) and acetylcholine (ACh; 3, 10 and 30 mug/min). Coronary blood flow (CBF) was evaluated by a Doppler guide wire. The patients were divided into 2 groups on the basis of ACh testing: one with coronary spastic angina (CSA) and one with non-CSA. The frequencies of the PON1 genotype in the CSA group did not differ significantly from those in the non-CSA group. In the non-CSA group, the patients were subdivided into 2 groups: a group with the Q/Q or Q/R genotypes and a group with the R/R genotype. The vasoconstrictive responses of the epicardial coronary artery to ACh were comparable between the Q/Q + Q/R and R/R groups. Also, the coronary vasodilations induced by BK in the R/R group were similar to those in the QR + QQ group. There were no significant differences in the CBF responses induced by BK or ACh between the Q/Q + Q/R and R/R groups. In conclusion, as estimated by BK and ACh testing, our findings suggest that PON1 genotypes may not play a critical role in the modulation of endothelial vasomotor function in the intact coronary circulation.