Epinephrine and β-adrenergic agonists (β1 and β2 for isoproterenol, β1 for dobutamine, β2 for salbutamol) stimulated K+ (or86Rb) influx mediated by the Na+-K+-2Cl−cotransporter and the Na+-K+pump in isolated colonic crypt cells. Preincubation with bumetanide abolished the epinephrine effect on the Na+-K+pump, suggesting that the primary effect is on the cotransporter. Maximal effect was obtained with 1 μM epinephrine with an EC50 of 91.6 ± 9.98 nM. Epinephrine-induced K+ transport was blocked by propranolol with an IC50 of 134 ± 28.2 nM. α-Adrenergic drugs did not modify K+ transport mechanisms. Neither Ba2+ nor tetraethylammonium nor DIDS modified the adrenergic enhancement on the cotransporter. In addition, epinephrine did not affect K+ efflux. Dibutyryl cAMP did not alter K+ transport. Reduction of extracellular Ca2+ to 30 nM did not influence the response to epinephrine. However, 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid-AM abolished epinephrine-induced K+ transport. Ionomycin increased Na+-K+-2Cl−cotransport activity. Moreover, epinephrine increased intracellular Ca2+ concentration in a process inhibited by propranolol. In conclusion, epinephrine stimulated the Na+-K+-2Cl−cotransporter in a process mediated by β1- and β2-receptors and modulated by intracellular Ca2+ liberation.