The present study was performed to determine the effects of intrarenal nNOS derived nitric oxide on afferent and efferent arteriolar responses to ANGII. Experiments were performed in vitro using the blood perfused juxtamedullary nephron technique combined with videomicroscopy. Kidneys were harvested from anesthetized, enalaprilat-treated male Sprague Dawley rats (350-400g). Afferent and efferent arteriolar reactivity to ANGII (0.1, 1, and 10nM) was assessed before and during the nNOS inhibition with 10μM S-methyl-L-thiocitrulline (L-SMTC) followed by total NOS blockade with 100μM nitro-L-arginine (NLA). Afferent and efferent arteriolar diameters averaged 22.1±0.7 (n=4) and 17.9±0.7 μm (n=4); respectively, and dose-dependently vasoconstricted to ANGII. ANGII (10 nM) decreased afferent and efferent arteriolar diameters by 35.3±3.0 and 31.6±1.8%; respectively. L-SMTC (10μM) significantly reduced basal diameter of afferent and efferent arterioles by 9.2±0.2 and 9.0±0.5%; respectively, and significantly enhanced efferent arteriolar responsiveness to ANGII. During exposure to L-SMTC, 10 nM ANGII decreased afferent and efferent diameters by 36.8±2.7 and 44.3±1.6%; respectively. NLA (100μM) decreased both basal diameters to a similar extent as L-SMTC. In contrast to the apparent predominant effect of L-SMTC on efferent reactivity to ANGII, NLA significantly enhanced both afferent (46.3±4.4%) and efferent (46.3±1.5%) reactivity to ANGII. These results indicate that intrarenal nitric oxide modulates ANGII-induced renal arteriolar vasoconstriction; however, nitric oxide derived from nNOS exerts a predominant modulating effect on efferent arteriolar responsiveness.