Hearts perfused in vitro with buffer containing glucose and amino acids developed a block in peptide-chain initiation associated with a decline in the rate of protein synthesis, increased ribosomal subunits, and decreased polysomes. Provision of insulin or palmitatealbumin prevented or reversed development of the initiation block. Protein synthesis in anoxic hearts was inhibited by a restricted rate of peptide-chain elongation; ribosome profiles were more aggregated than those of control tissues. High-energy phosphate levels were reduced 50% by anoxia. Release of" C-phenylalanine during perfusion reflected the rate of protein degradation. Net release of phenylalanine indicated that the rate of protein degradation exceeded that of synthesis in control hearts. Provision of insulin completely prevented or reversed this imbalance; palmitate was only partially effective. Since increased phenylalanine release was associated with increased numbers of autophagic vacuoles, cathepsin-D activity was estimated.“Available” activity increased from 20% to 33% of total during 3 hours of perfusion. Insulin prevented or reversed this increase. Thus, a balance in protein turnover was maintained through concomitant effects of insulin to increase protein synthesis and to reduce protein degradation. These effects involved changes in ribosome cycle and lysosomal enzyme activities.