Epinephrine and -adrenergic agonists (₁ and ₂ for isoproterenol, ₁ for dobutamine, ₂ for salbutamol) stimulated K⁺ (or ⁸⁶Rb) 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. -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 ₁- and ₂-receptors and modulated by intracellular Ca²⁺ liberation.