In vitro experiments showed that the connecting tubule (CNT) sends a signal that dilates the afferent arteriole (Af-Art) when Na ϩ reabsorption in the CNT lumen increases. We call this process CNT glomerular feedback (CTGF) to differentiate it from tubuloglomerular feedback (TGF), which is a cross talk between the macula densa (MD) and the Af-Art. In TGF, the MD signals the Af-Art to constrict when NaCl transport by the MD is enhanced by increased luminal NaCl. CTGF is mediated by CNT Na ϩ transport via epithelial Na ϩ channels (ENaC). However, we do not know whether CTGF occurs in vivo or whether it opposes the increase in Af-Art resistance caused by TGF. We hypothesized that CTGF occurs in vivo and opposes TGF. To test our hypothesis, we conducted in vivo micropuncture of individual rat nephrons, measuring stop-flow pressure (P SF) as an index of glomerular filtration pressure. To test whether activation of CTGF opposes TGF, we used benzamil to block CNT Na ϩ transport and thus CTGF. CTGF inhibition with the ENaC blocker benzamil (1 M) potentiated the decrease in P SF at 40 and 80 nl/min. Next, we tested whether we could augment CTGF by inhibiting NaCl reabsorption in the distal convoluted tubule with hydrochlorothiazide (HCTZ, 1 mM) to enhance NaCl delivery to the CNT. In the presence of HCTZ, benzamil potentiated the decrease in P SF at 20, 40, and 80 nl/min. We concluded that in vivo CTGF occurs and opposes the vasoconstrictor effect of TGF. afferent arteriole; macula densa; connecting tubule; glomerular filtration rate; sodium ion transport; benzamil; stop-flow pressure WE AND OTHERS HAVE SHOWN that, in the renal cortex, the connecting tubule (CNT), a segment of the nephron located between the distal convoluted tubule and collecting duct, returns to the vascular pole of the glomerulus and accompanies the afferent arteriole (Af-Art) for varying distances (2,6,7,28). This morphology is compatible with cross talk between the CNT and the Af-Art. In vitro experiments showed that the CNT sends a signal that dilates the Af-Art when Na ϩ reabsorption in the CNT increases. We called this process CNT glomerular feedback (CTGF) to differentiate it from tubuloglomerular feedback (TGF), which is cross talk between the macula densa (MD) and the 24). From a homeostatic point of view, TGF is a negative feedback loop that senses increases in NaCl at the MD and increases Af-Art resistance while at the same time decreasing glomerular filtration rate (GFR), thus favoring Na ϩ retention. On the other hand, CTGF is a positive feedback loop that decreases Af-Art resistance in response to increases in NaCl in the CNT. A decrease in Af-Art resistance increases both renal blood flow and GFR and thus favoring Na ϩ excretion. NaCl reabsorption is mediated by the thiazide-sensitive Na ϩ -Cl Ϫ cotransporter (NCC) in the distal convoluted tubule and the amiloride/ benzamil-sensitive epithelial Na ϩ channel (ENaC) in the CNT and cortical collecting duct (17,18,21). Thus benzamil blocks CTGF (23) while hydrochlorothiazide (HCTZ), by block...