Ionic transport in macula densa cells. Recent work has provided substantial insights into functional characteristics of macula densa (MD) cells. Microelectrode and patch-clamp experiments on the rabbit isolated thick ascending limb (TAL)/glomerulus preparation have shown that MD cells possess a furosemide-sensitive Na: K: 2Cl cotransporter, an apical 41-pS K+ channel, and a dominant basolateral Cl-conductance. Increasing luminal fluid [NaCl]([NaCl] L) results in furosemide-sensitive cell depolarization due to a rise in intracellular [Cl-] that stimulates basolateral electrogenic Cl-efflux. Intracellular pH (pH i) measurements show the presence of an apical Na: H exchanger that couples transepithelial Na+ transport to pH i. Experimental results and thermodynamic considerations allow estimation of intracellular [Na+] and [Cl-]([Na+] i,[Cl-] i) under different conditions. When the Na: K: 2Cl cotransporter is equilibrated (or in the presence of furosemide),[Na+] i and [Cl-] i are low (∼ 6 to 7 m m), whereas when the cotransporter is fully activated,[Na+] i and [Cl-] i increase substantially to approximately 70 and 20 m m, respectively. Finally, luminal addition of NH 4+ produces cell acidification that depends on NH 4+ apical transport rate through the Na: K: 2Cl. Using a simple transport model for NH 4+, the initial NH 4+ influx rate in MD cells is comparable to the corresponding flux in TAL. This challenges the idea that MD cells have a low transport activity but supports our findings about large changes in intracellular concentrations as a function of [NaCl] L.