The rate of amino acid incorporation by liver microsomes from young, adult and old rats has been investigated, and a gradual decline of this rate has been observed. Further, an inhibitory effect of the cell sap on amino acid incorporation by liver microsomes and an increase of this effect with age of the animal have been demonstrated. The results are consistent with the presence of inhibitors of protein synthesis in liver microsomes and in liver cell sap and with the gradual accumulation of these inhibitors during growth cessation and aging. The nature and mechanism of these inhibitors are discussed within the framework of currently available evidence. It is suggested that a gradual accumulation of humoral inhibitory substances of protein character leads to a gradual accumulation of inhibitors in the cell sap and in the microsomal vesicles, i.e., in the endoplasmic reticulum, and thus to a gradual repression or feedback inhibition of protein synthesis at the site of translation of genetic messages into protein, wich in turn represses RNA synthesis and DNA replication and is one of the major factors of growth cessation and aging. © 1969 S. Karger AG, Basel.