The rate of degradation of cell proteins in Escherichia coli was studied under various conditions that affect levels of charged tRNA. Protein breakdown increased markedly when the synthesis of valyl-tRNA was prevented in strains containing temperature-sensitive valyl-tRNA synthetase or when the formation of N-formylmethionyl-tRNA was inhibited with trimethoprim. Conversely, protein breakdown decreased in a valine auxotroph-administered valine or an analog capable of attachment to the valyl-tRNA. It appears that changes in the levels of aminoacyl-tRNA regulate protein breakdown by mechanisms similar to those controlling the synthesis of ribosomal RNA. These experiments also demonstrate that protein synthesis is not essential for protein degradation and suggest that the inhibition of degradation in starving cells by chloramphenicol is a secondary effect of the accumulation of charged tRNA.