22Na+ and 36Cl- fluxes across isolated reticular epithelium of sheep were measured by using the Ussing-chamber technique. 2. Net NaCl absorption driven by Na(+)-K(+)-ATPase was observed under short-circuit conditions. 3. Evaluation of fluxes measured under voltage-clamp conditions indicated that Na+ absorption is mainly electroneutral. 4. Mucosal application of bumetanide, hydrochlorothiazide, or low dose amiloride (10(-4) M) produced no changes in Na+ transport whereas addition of higher doses of amiloride (> or = 10(-3) M) led to a reduction in net Na+ transport. Short chain fatty acids (SCFA) enhanced the amiloride-sensitive Na+ transport. 5. Alterations of JmsNa induced by inhibitors or by SCFA were always accompanied by qualitatively similar changes of JsmNa. Amiloride-sensitive JsmNa was also decreased at low mucosal Na+ concentration. 6. DIDS, SITS, and nitrate reduced both JmsCl and JsmCl. SCFA did not influence chloride transport. 7. It is concluded that Na+ transport is mediated by Na(+)-H+ exchange and by transport processes operating as Na+ self-exchange. Mucosal-to-serosal chloride transport seems partly to depend on anion exchange systems.