In vivo studies have shown that ammonium is secreted into the lumen of each of the major collecting duct segments. This secretion occurs by passive diffusion of NH3 in parallel with active H+ secretion. In vitro measurements in each segment have established that the NH3 permeability is relatively high (10(-3) to 10(-2) cm/s) while the NH4+ permeability is essentially zero. Interstitium to lumen NH3 concentration gradients have been observed in vivo in the inner medulla and are presumed to exist in other segments. The active H+ secretion causes a pH disequilibrium in segments which lack carbonic anhydrase and enhances the NH3 gradient driving NH3 secretion by decreasing the luminal NH3 concentration. The low NH4+ permeability prevents NH4+ backflux.