The study was undertaken to examine the intensity of involvement of inducible nitric oxide synthase(iNOS) and cyclic GMP signal transduction pathway as one of the mechanisms of vaso-relaxative action of bacterial lipopolysaccharide (LPS) on the canine femoral artery strips. Canine femoral arteries were isolated and spiral strips of 10 mm long and 2 mm wide were made in the Tyroad solution of 0-4degrees C. The strips were prepared for isometric myography in Biancani's isolated muscle chamber contaning 1 ml of Tyrode solution, which was maintained with pH 7.4 by areation with 95% O2/5% CO2 at 37degrees C and nitric oxide (NO) production was measured simulltaneously with isolated nitric oxide mrter. LPS induced NO production, suppressed the phenylephrine (PE) induced contraction and enhanced the acetylcholine (ACh) induced relaxation. NG-nitro-L-arginine methyl ester (L-NAME), an NOS inhibitor, methylene blue, a guanylyl cyclase inhibitor, potentiated PE induced contraction and suppressed ACh induced relaxation on the LPS treated strips. The inhibitory potency of methylene blue for LPS induced vascular hyporeponsiveness was stronger than that of L-NAME. These result suggest that in canine femoral artery, both iNOS and cyclic GMP signal transduction pathway are related with LPS indused vascular hyporeponsiveness, but in minor with iNOS and in major with cyclic GMP signal transduction pathway.