Sodium chloride transport across isolated cecum mucosa was investigated in normal rats and rats with adaptive cecum growth induced by dietary polyethylene glycol (PEG). The normal cecum absorbed CI in excess of Na with a small short-circuit current (Isc). Dietary adaptation led to large equivalent increments of Na and Cl net absorption without adequate Ise change. Inhibitor studies (mucosal amiloride 10(-3) and 10(-4) M; mucosal 4,4-diisolhiocyanatostilbene-2,2-disulfonic acid 5 x 10(-5) M;serosal furosemide 10(-3) M;serosal ouabain 10(-3) M) suggested that normal cecal NaCl absorption involves electroneutral Na/N and Cl/HCO3 exchange at the apical and Na-K-ATPase-mediated exit across the basolateral cell membrane. Dietary adaptation stimulates the loosely coupled antiports and possibly activates a small serosally located NaCl cotransport. Comparative histology showed flattening of all tissue layers and widening of crypts in PEG animals. Crypt widening may facilitate ion access to underutilized transport sites and, at least in part, explain the increased absorption of the enlarged cecum.