The translation of natural messenger RNA (e.g. T4 mRNA or MS2 RNA) requires the presence of three specific protein factors, A, B and C, which are not necessary for poly U translation. Factor C appears to act on the binding of ribosomes to the mRNA chain while factors A and B are involved in the fixation of the initiator tRNA, formylmethionyl-tRNA, to the ribosome-mRNA complex. The function of factor C was particularly clear in the binding of ribosomes to nascent RNA produced on T4 DNA by Escherichia coli RNA polymerase. Binding of 30 s ribosomal subunits to nascent T4 mRNA required the presence of factor C as shown by direct electron microscopic observation of the formation of DNA-RNA-ribosome complexes. Factor C-dependent ribosome binding to nascent RNA was accompanied by a stimulation of the transcription process; longer chains of RNA were produced and RNA molecules were released from the DNA template. The three factors were found to be localized in a cell fraction in which ribosomes are associated with DNA, suggesting that in vivo they participate in the initiation of protein synthesis on messenger RNA before its release from the DNA template.