Currently available data on the effect of age in tissue protein synthesis and turnover are reviewed and experimental evidence is presented on age changes in amino acid incorporation by rat liver purified microsomes. It has been observed that the purification of ‘crude’ microsomal preparations from contaminating lysosomes by density gradient centrifugation is accompanied by an increase in amino acid incorporatmg activity of the microsomal preparations, no matter whether these are prepared from young or from old animals, and that the amino acid incorporating activity of rat liver purified microsomes prepared from old animals (19–25 months) is lower than that prepared from adult animals (7–11 months) which in turn is lower than that from young animals (2–3 months), no matter whether the activity is expressed per mg of microsomal protein or per mg of microsomal RNA. Also, experimental evidence is presented which is consistent with the presence in liver purified microsomes of heat-labile inhibitor(s) of amino acid incorporation, and with their accumulation (or increase in effect) in the microsomes with the age of the animal. Several major features of the decline with age in tissue protein synthesis are outlined and a number of possible factors or causes, beside the microsomal inhibitor(s), contributing to the decline with age in tissue protein synthesis, are discussed.