By using micropuncture technique and measuring inulin concentrations in plasma and tubular fluid, and tubular flow rate, single nephron glomerular filtration rate (SNGFR) was calculated. The effect of stimulation of the brain osmoreceptors on the sensitivity of tubulo-glomerular feedback in rats was observed. The SNGFR value measured at the proximal tubular (SNGFRp) was greater than that measured at the distal tubule (SNGFRd) of the same nephron. The difference between these two values (SNGFRp-d) was a measure of the extent of tubuloglomerular feedback (TGF). The SNGFRp-d value was reduced after intracerebroventricular administration of hypertonic saline (icv. HS), indicating that stimulation of the brain osmoreceptor can attenuate the sensitivity of TGF. The icv. HS-induced increase in renal plasma flow rate and glomerular filtration rate could be abolished by intravenous injection of furosemide, while natriuretic response persisted. These results suggest that icv. HS can alter renal hemodynamics via reduction of TGF, and confirm the claim that icv. HS can inhibit tubular reabsorption, which is responsible for the natriuretic response.