The mouse is the model of choice in studies of physiology and pathophysiology of intestinal electrolyte transport. We have observed differences in electrical tissue properties and responses to agonists that induce electrogenic secretion of electrolytes among mice strains, that are important enough to preclude comparisons between strains and might be crucial when choosing the genetic background for knockout of genes of interest. We have investigated some of these differences by electrophysiological methods. A piece of distal colon of B6, Black Swiss or 129 Sv mice was placed in Ussing chambers in a bicarbonate buffered solution, gassed with 95% O₂/5% CO₂ at 37^○ C. The transepitheial potential difference was monitored continuously and 5 μA pulses were passed to calculate tissue resistance and equivalent short circuit current (Isc). To induce cAMP-mediated Cl^– secretion 100 μM IBMX and 1 μM forskolin were added. Bumetanide (100 μM) was added to the basolateral side of the tissue to block NKCC1 co-transporter. Apical Ba²⁺ (5 mM) inhibited K⁺ channels. Basolateral carbachol (100 μM) or Histamine (150 μM) were used as Ca²⁺ agonists. 4-DAMP, Pirenzepine and Mepyremine are M3, M1 and H1 receptors blockers respectively. Animals were killed under IUCAC regulations and approval of the ethical committee. We observe that CCH induced the largest anionic secretory response in B6 tissue, compared to that of Black Swiss and 129Sv colon (-200, -163 and -133 μA cm^-2 respectively). The use of blockers for muscarinic and histaminergic repector indicated that M3 and H1 receptors were involved in the secretory responses in all types of colon. Histamine was able to induce K⁺ and Cl^– secretory responses in the B6 colon while in the other two only K⁺ secretion was observed. By adding Ba²⁺ to the mucosal side of the chamber a K⁺ secretory process was blocked, and shown to be larger in the 129 Sv colon (15 ± 1.2 μA cm^-2) compared to B6 and Black Swiss (both around 10 μA cm^-2). Bumetanide inhibits K⁺ secretion in Sv 129 colon only. In all strains K⁺ secretion was activated by cAMP. RT-PCR studies demonstrated the presence of 2 KCNMA1 splice variants in colon: ZERO and STREX. We conclude that the observed differences in calcium-activated K⁺ and Cl^– secretion are not due to the presence of different receptors among strains. The cAMP dependence of K⁺ secretion suggests that the ZERO variant of KCNMA1 is active in colon, rather than STREX that is inhibited by cAMP. A difference in the number of channels involved in these processes cannot be discarded as we have previously observed that the calcium-activated Cl^– secretion is dependent on the expression level of basolateral KCNN4 channel rather than apical CFTR channels. Our results also show the importance of the genetic background in determining intestinal transport properties.