Investigations on the absorption of shortchain fatty acids across ruminal epithelium of sheep were performed both in vitro (Ussing chamber technique, using propionic acid representatively for shortchain fatty acids) and in vivo (washed, isolated reticulorumen). A pH-induced, nearly tenfold increase in the concentration of undissociated propionate led to an only twofold increase in mucosal-to-serosal flux of propionate (in vitro). Neither amiloride (1 mmol·l, in vitro) nor theophylline (10 mmol·l, in vivo), inhibitors of the ruminal Na/H exchanger, exerted any significant influence on propionate fluxes or short-chain fatty acids absorption, respectively. Total replacement of luminal Na (by choline) did not alter short-chain fatty acids absorption (in vivo). Mucosal 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (0.1 mmol·l) or mucosal nitrate (40 mmol·l) markedly reduced propionate net flux (in vitro). Increasing mucosal Cl concentration brought about a significant drop in mucosal-to-serosal flux of propionate (in vitro) and in short-chain fatty acids net absorption (in vivo), respectively. The results obtained suggest that short-chain fatty acids are absorbed both as anions and as undissociated acids across ruminal epithelium of sheep. It is concluded that short-chain fatty acids anions either compete with Cl for binding sites at a common anion-exchange mechanism or that they are absorbed by an short-chain fatty acids anion/HCOexchanger indirectly coupled to a Cl/HCOexchanger via intracellular bicarbonate. [ABSTRACT FROM AUTHOR]