Nitric oxide is produced by the NO synthase, which catalyses the conversion of arginine to citrulline and NO using tetrahydrobiopterin as an essential cofactor. N-Acetylserotonin, an inhibitor of the tetrahydrobiopterin biosynthesis, given 30 min before bacterial lipopolysaccharide to anesthetized rats, inhibited both the decrease in blood pressure and the increase in nitrite plasma levels induced by lipopolysaccharide. Thus, during endotoxemia the availability of tetrahydrobiopterin appears to be essential for the activity of NO synthase.