Transepithelial transport in the rabbit distal colon surface cells involves the integrated function of amiloride-sensitive Na+ channels in the luminal membrane and the Na, K-pump, together with K+ channels in the basolateral membrane. Incorporation of plasma membrane vesicles from surface cells into planar lipid bilayers shows that a Ca(2+)-activated maxi K+ channel with a single channel conductance of approximately 275 pS is predominant in the basolateral membrane of this cell type. The epithelial Ca(2+)-activated maxi K+ channels are regulated by Ca2+ in the intracellular range of concentration, pH, and membrane potential. The high Ca(2+)-sensitivity of the epithelial maxi K+ channels is dependent on the channel protein being in a phosphorylated state. Dephosphorylated channels can regain their Ca(2+)-sensitivity after phosphorylation catalyzed by a cAMP dependent protein kinase. The extensive regulation of the epithelial maxi K+ channels by intracellular factors suggests that these channels may play an important role in regulation of transepithelial transport and may be one explanation for the apparent tissue to tissue variability in properties for this channel type.