The eukaryotic initiation factor (eIF) 4F complex is composed of three polypeptides: eIF4A, eIF4E and eIF4G. eIF4E is the cap-binding subunit; eIF4A is the component which exhibits RNA helicase activity and is thought to unwind the secondary structure present at the 5' leader sequences of mRNAs; eIF4G serves as a scaffold to bring together eIF4E, eIF4A, with eIF3, thus recruiting the mRNA to the 40S small ribosomal subunit. Here, I describe the identification and characterization of a novel homologue of eIF4G that we have termed eIF4GII. We renamed the previously discovered polypeptide, eIF4GI. eIF4GI and eIF4GII are 46% identical at the amino acid level. eIF4GII interacts directly with eIF4E, eIF4A, eIF3 and the poly(A) binding protein. eIF4GII restores cap-dependent translation in a reticulocyte lysate which had been pretreated with rhinovirus 2A protease to cleave endogenous eIF4G. Our findings indicate that eIF4GII is a functional homologue of eIF4GI.