This study explores the nature of K fluxes in human lens epithelial cells (LECs) in hyposmotic solutions. Total ion fluxes, Na/K pump, Cl-dependent Na-K-2Cl (NKCC), K-Cl (KCC) cotransport and K channels were determined by ⁸⁵Rb uptake and cell K (K_c) by atomic absorption spectrophotometry, and cell water gravimetrically after exposure to ouabain ± bumetanide (Na/K pump and NKCC inhibitors) and ion channel inhibitors in varying osmolalities with Na, K or methyl-D-glucamine and Cl, sulfamate or nitrate. Reverse transcriptase polymerase chain reaction (RT-PCR), Western blots and immunochemistry were performed. Results show in isosmotic (300 mOsM) media ~90% of the total Rb influx occurred through Na/K pump and NKCC, ~ 10% through KCC and a residual leak. Hyposmotic media (150 mOsM) decreased K_c by a 16-fold higher K permeability, lowered cell water but failed to inactivate NKCC and activate KCC. Sucrose replacement or extracellular K, but not Rb or Cs, to >57 mM in hyposmotic media prevented K_c and water loss. Rb influx equaled Kc loss, both blocked by clotrimazole (IC50 ~25 µM), and partially by TRAM-34 [1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole], inhibitors of the IK channel, K_Ca3.1, but not by other K channel or connexin hemichannel blockers. Of several anion channel blockers, DIOA [(dihydro-indenyl)oxy]alkanoic acid], DCPIB [4-2(butyl-6,7-dichloro-2-cyclopentylindan-1-on-5-yl)oxybutyric acid] and phloretin totally or partially inhibited K_c loss and Rb influx, respectively. RT-PCR and immunochemistry confirmed presence of K_Ca3.1 channels, aside of the KCC1,2,3 and 4 isoforms. Apparently, IK channels, possibly in parallel with volume-sensitive outwardly rectifying Cl channels effect regulatory volume decrease in LECs.