Bicarbonate presence in the bathing media doubles Na+ and fluid transepithelial transport and in parallel significantly increases Na+ and Cl- intracellular concentrations and contents, decreases K+ cell concentration without changing its amount, and causes a large cell swelling. Na+ and Cl- lumen-to-cell influxes are significantly enhanced, Na+ more so than Cl-. The stimulation does not raise any immediate change in luminal membrane potential and cannot be due to a HCO3--ATPase in the brush border. The stimulation goes together with a large increase in a Na+-dependent H+ secretion into the lumen. All of these data suggests that HCO3- both activates Na+-Cl- cotransport and H+-Na+ countertransport at the luminal barrier. Thiocyanate inhibits Na+ and fluid transepithelial transport without affecting H+ secretion and HCO3--dependent Na+ influx. It reduces Na+ and Cl- concentrations and contents, increases the same parameters for K+, causes a cell shrinking, and abolishes the lumen-to-cell Cl- influx. It enters the cell and is accumulated in the cytoplasm with a process which is Na+-dependent and HCO3--activated. Thus, SCN- is likely to compete for the Cl- site on the cotransport carrier and to be slowly transferred by the cotransport system itself. © 1979 Springer-Verlag New York Inc.