Nitric oxide (NO) plays an important role in controlling the physiological functions of the cardiovascular system. However, toxic peroxynitrite is produced by the reaction of NO with superoxide. We investigated the effect of aged garlic extract (AGE) on NO production, and on oxidative stress induced by peroxynitrite. A single dose of AGE temporarily increased NO production by 30-40% between 15 and 60 min after administration to mice. The time course of the fluctuation in NO levels in the AGE-treated group clearly differed from that in a group treated with an inducible NO synthase (iNOS) inducer. A selective constitutive NOS (cNOS) inhibitor overcame the effect of AGE. These results indicate that AGE increases NO production by activating cNOS, but not iNOS. In another experiment, the addition of AGE to a rat erythrocyte suspension reduced the rate of peroxynitrite-induced hemolysis in a concentration-dependent manner, suggesting that AGE protects erythrocytes from membrane damage induced by peroxinitrite. Because an increase in NO derived from cNOS and protection against peroxynitrite are important factors in the prevention of cardiovascular disease, our data strongly suggest that AGE could be useful in preventing cardiovascular diseases associated with oxidative stress or dysfunctions of NO production.