Rabbit cecum exhibits electrogenic Na absorption in vitro. However, because this transport process is not inhibited by amiloride nor does it demonstrate saturation kinetics typical of the amiloride-inhibitable Na channel, we considered whether the cecal transporter represented one of a recently described family of nonselective cation conductances or channels (NSCC). Both transepithelial and vesicle studies demonstrated that K, Cs, and Rb were transported via an apical conductance. Electrogenic transport was inhibited by divalent cations including Ca, Mg, and Ba but was unaffected by either lanthanum or gadolinium. Parallel studies in distal colon did not exhibit a similar response to either K substitution or Ba inhibition. Phenamil, verapamil, and nicardipine significantly inhibited the short-circuit current (Isc). stimulated by nominal Ca- and Mg-free conditions. Flux studies demonstrated a correlation between changes in Isc and Na transport. Microelectrode impalement studies suggested that there may be both NSCC and K conductance in the apical membrane. Planar bilayer studies identified a 190-pS cation channel that may correlate with the macroscopic transport properties of this epithelium. These studies are consistent with a model of cecal Na absorption mediated by a NSCC in the apical membrane; this may be the mechanism underlying the distinct epithelial transport characteristics of this intestinal segment.