Recent reports indicated that vaccinia virus late mRNAs contain a unique 5' poly(A) leader sequence and that the in vitro translation of these mRNAs may be relatively cap-independent. These observations led us to examine the possibility that the mechanism of inhibition of host protein synthesis by vaccinia virus, like that of certain other viruses, involves specific modifications of the cap-binding translation initiation factor complex eIF-4F. The eIF-4F complex was affinity-purified from human cells infected with vaccinia virus and analyzed by one- and two-dimensional electrophoresis and immunoblotting. No evidence of vaccinia virus-induced degradation of p220, as occurs during poliovirus infection, or alteration of phosphorylation of eIF-4E (p24), as occurs during adenovirus infection, was detected at the time of severe inhibition of host protein synthesis.