A primary event in the stimulation of cyclic AMP-mediated active Cl secretion across epithelial tissues is an increase in the Cl permeability of the apical cell membrane. A rapid reduction in apical cell membrane resistance to Cl movement permits Cl to leave the cell down its electrochemical potential difference across this barrier. Since cell Cl activity is not markedly influenced by changes in the rate of Cl secretion, the cyclic nucleotide may also increase the ease with which Cl gains access to the secretory cells across the basolateral membrane. This Cl entry process appears to be mediated by NaCl co-transport since the maintenance of a high cell Cl activity depends upon the presence of sodium in the serosal bathing solution. Increased Cl entry across the basolateral membrane would promote enhanced Na entry into the cell and a secondary stimulation of active Na extrusion from cell to serosal solution. Increased Na-K-pump activity and/or a change in the K permeability of the basolateral membrane may be responsible for the augmented conductive ion flow across this barrier which accompanies the stimulation of active Cl secretion.