Oxidation of branched-chain amino acids, leucine, isoleucine and valine, is thought to occur primarily in muscle. Theoretically, however, it is possible for valine carbon to be converted to glucose, a process which only occurs in liver and kidney. We provide evidence that valine is oxidixed toβ-hydroxyisobutyrate in muscle, and that this intermediate is released from muscle and taken up by liver and kidney for subsequent conversion to glucose, thus conserving the gluconeogenic potential of valine.