Electrogenic Na⁺-transport across rumen epithelium occurs via a non-selective cation channel, blocked by luminal Ca²⁺ and Mg²⁺ and by cytosolic Mg²⁺. The role of protein kinase C (PKC) in the regulation of this pathway was studied with isolated epithelia from goat rumen incubated in Ussing chambers. Omission of Ca²⁺ and Mg²⁺ from the luminal side induced an increase in short circuit current followed by a decline. This down-regulation of Na⁺-current was delayed after activation of PKC with 6-[N-decylamino]-4-hydroxymethylinole. Na⁺-current declined again after inhibition of PKC with chelerythrine, showing that PKC contributes to the regulation of ruminal electrogenic Na⁺-transport.