Evidence from many lines of investigation suggest a complex role for the sequences at the 5 feet-terminus of eukaryotic mRNAs in determining the efficiency with which translation is initiated. We propose to systematically mutate in vitro the gene for a specific adenovirus type 5 mRNA, reincorporate the mutated gene into the viral genome and then measure the effect of the various mutations on the efficiency of translation of the mutated mRNA using an in vivo assay which has been developed in this lab. This approach will define the sequences at the 5 feet-terminus of mRNAs which are important in determining the efficiency of translation under physiological conditions.