Factors that provide translational control of protein synthesis by inhibiting peptide initiation in rabbit reticulocytes are being isolated and characterized with respect to their physical properties and function. It is apparent from work completed to date that a number of enzymes may function sequentially in the presence of heme to activate the eIF-2alpha kinase that may also be activated in the absence of heme. This kinase is part of the hemin-controlled repressor or HCR system. The eIF-2alpha kinase itself appears to be a 100,000 dalton peptide and to require phosphorylation for activity. A 90,000 dalton peptide apparently is a constituent part of the kinase for the 100,000 dalton peptide. A heat-stable component, HS, that can be reversibly activated by heat or pressure functions at the distal end of the cascade type reaction sequence for activation of eIF-2alpha kinase. This factor with ATP functions to irreversibly activate a heat labile component, HL, that functions directly or indirectly in the activation of the 90,000 dalton kinase or the 100,000 dalton eIF-2alpha kinase. A protein phosphates that dephosphorylates eIF-2alpha or the 100,000 dalton peptide ofthe eIF-2alpha kinase also has been partially purified and characterized.