NaCl and Na/K/Cl co-transport systems in many cell types show a number of similarities, among which are sensitivity to ‘loop’ diuretic inhibition and extremely high anion selectivity. Avian erythrocytes possess a NA+K+2Cl co-transporter that is stimulated by agents raising intracellular cAMP. The system is also inhibited following ATP-depletion of the cells, in agreement with results in other tissues; this nucleotide may exert a regulatory role on the operation of the co-transporter. A Na/K/Cl co-transport system is also present in flounder intestine, where it plays a central role in salt absorption at the luminal border of the tissue. In contrast to the avian erythrocyte this system is inhibited by raising intracellular cyclic nucleotide content, cGMP being more effective than cAMP. From these results it is concluded that second messenger regulation of Na/K/Cl co-transport processes is heterogeneous and may exhibit some tissue specificity.