In colon the crypts are the site of Cl^-secretion. Transcellular Clsecretion occurs via basolateral (bl.) NKCC1-mediated uptake and subsequent CFTR-mediated Cl^-exit. Bl. K⁺ channels are essential for sustained Cl^-secretion. Relevant colonic epithelial K⁺ channels are the Ca²⁺-activated SK4 channel (KCNN4) and the cAMP-activated KCNQ1 channel. Also BK channels were suggested to play a role in Ca²⁺-activated Cl^-secretion. Here we use BK and SK4 knock-out mice to investigate the role of these K⁺ channels in Ca²⁺ agonist (carbachol, CCH) stimulated Clsecretion. An Ussing chamber was used to quantify agonist-stimulated increases in short circuit current in distal colon. Clsecretion was activated by bl. forskolin (1mM) followed by bl. CCH (100mM). In BK WT mice forskolin followed by CCH increased Isc by 121.6±25.0 and further by 188.2±20.3 mAcm ^­2 (n=10). Similar results were measured in BK KO mice ([Delta]Isc FOR 121.6±25.2 and [Delta]Isc CCH: 181±32.8 mAcm ^­2(n=12). In SK4 WT mice [Delta]Isc FOR was 79.5±14.0 followed by [Delta]Isc CCH of 203.1±18.3 mAcm ^­2 (n=5). In SK4 KO mice [Delta]Isc FOR was similar with 78.1±21.0 mAcm ^­2. However, [Delta]Isc CCH was greatly reduced to 88.7±10.0 mAcm ^­2, n=5). These results underscore the importance of basolateral SK4 channels for Ca²⁺-activated Clsecretion in mouse distal colon. In contrast, no role for BK channels in Ca²⁺-activated Cl^-secretion was found.