Vaccinia viral core inhibits protein synthesis in heme-supplemented reticulocyte lysate. A reticulocyte cell suPernatant factor, which reversed Protein synthesis inhibition in heme-deficient reticulocyte lysate also reversed vaccinia viral core induced Protein synthesis inhibition in heme-suPPlemented reticulocyte lysate. Significant inhibition reversal activity was also observed with a partially purified eukaryotic initiation factor-2 PreParation and this activity was lost uPon further Purification of eukaryotic initiation factor-2.The ribosomal salt-wash factor Co-eukaryotic initiation factor-2 which like reticulocyte suPernatant factor contains guanine nucleotide exchange factor activity, was comPletely inactive. Vaccinia viral core induced detectable level of eukaryotic initiation factor-2 α-subunit phosphorylation when incubated in the heme-supplemented reticulocyte lysate. This lysate preparation contains guanine nucleotide exchange factor activity. However, when the same reticulocyte lysate was previously incubated with the vaccinia viral core, the guanine nucleotide exchange factor activity during subsequent incubation was almost comPletely inhibited.