As single-nephron glomerular filtration rate (SNGFR) and late proximal flow (VLP) increase during growth or following volume expansion, the tubuloglomerular feedback (TGF) function (defined as the decrement in SNGFR due to the process of TGF) shifts rightward in the plane defined by VLP and SNGFR as required to maintain the homeostatic efficiency of TGF. It is not known whether this resetting of TGF requires changes in the systemic hormonal milieu or results from prolonged activation of TGF itself. We employed micropuncture and videometric flow velocitometry (an optical technique for measuring flow in unobstructed nephrons) to address this issue in Inactin-anesthetized euvolemic rats. The fractional compensation (C) of TGF for perturbations [late proximal flow perturbation (VH) = +/- 5 nl/min] in VLP was assessed repeatedly before and during a sustained increase in flow imposed by adding 20 nl/min to early proximal flow (VEP). Augmenting VEP initially saturated TGF, thus suppressing C. Over the next 30 min, C recovered to 70% of its original value, suggesting a rightward resetting of the TGF function to match the increase imposed on VLP. Resetting was confirmed by documenting an evolving asymmetry of C about VH = 0 by testing C vs. VH for -12 < or = VH < or = 12 in increments of 4 nl/min. Beyond 30 min of augmented VEP, C gradually declined due to desensitization of TGF. A sustained increase in VLP is sufficient to include TGF resetting, independent of any change in the systemic neurohumoral milieu.