Electrogenic, cAMP-mediated Cl secretion across rabbit descending colon in vitro is independent of the rate or presence of active Na absorption. Yet, several observations indicate that this process is Na dependent: a) Cl secretion requires the presence of Na in the serosal solution alone, b) the kinetics of Cl transport as a function of external Na concentration are virtually identical to the Cl concentration dependence, and c) exchange of cell Cl with isotopic Cl added to the serosal solution is inhibited by Na-free media and by addition of furosemide to the serosal solution; the diuretic also inhibits Cl secretion. These findings suggest that Cl entry into the secretory cells across the basolateral membrane is mediated by NaCl cotransport. Addition of ouabain to, or removal of K from, the serosal solution inhibits Cl secretion so that Na entering the secretory cell across the basolateral membrane may be returned to the serosal solution by the Na-K pump. Finally, increasing the K concentration of the serosal solution inhibits Cl secretion under short-circuit conditions. This appears to result from K-induced depolarization of the electrical potential difference across the apical membrane so that diffusional Cl exit from cell to mucosal solution is reduced.