We have cloned and characterized a family of mouse genomic sequences hybridizing to mouse cDNA probes coding for eIF-4A, one of the protein synthesis initiation factors involved in the binding of mRNA to the ribosome. We estimate that there is a total of approximately 9-13 eIF-4A pseudogenes. We also found an eIF-4A intronless retroposon which, when compared to the cDNA, contains a single nucleotide difference. This possibly functional gene contains a mouse repetitive B1 element integrated in the promoter region. Furthermore, we have cloned two intron-containing eIF-4A genes (termed eIF-4AI and eIF-4AII). The eIF-4AII gene codes for a previously unknown form of eIF-4A. Northern blot hybridization with RNA from several mouse organs shows a variation in eIF-4AI expression within a factor of 7. In contrast, relative to liver, eIF-4AII expression is 20- to 30-times higher in brain and kidney, 10- to 17-fold higher in lung and heart, and is about equally abundant in liver, spleen and thymus. These data suggest that the relative efficiency of protein synthesis initiation for different mRNAs, as reflected by discrimination in messenger 5'-terminal cap recognition and binding to ribosomes, varies in different tissues.