On evolutionary grounds, it has been advocated for more than 40 years that RNA generally, and more recently rRNA in particular, may participate, catalytically, in protein biosynthesis. A specific molecular mechanism has never been proposed. We suggest here that the N-1 position(s) in one or more of the approximately 4 pseudouridine (omega) residues in E. coli 23 S rRNA catalyzes transfer of the aminoacyl moiety from teh 3'-terminus of peptidyl tRNA in the P site to aminoacyl tRNA in the A site of the ribosome. Evidence that supports the proposal in the case of E. coli ribosomes, and relevant information pertaining to eukaryotic ribosomes, is summarized. Essential features of the evidence are that (i) the N-1 position in 1-acetylthymine (a direct analogue of 1-acetylpseudouridine) has an especially high potential for acyl-group transfer, comparable to that found for N-acetylimidazole (Spector, L.B. and Keller, E.B. (1958) J. Biol. Chem. 232, 185-192), (ii) most of the omega residues in prokaryotic 23 S rRNA are confined to the peptidyl transferase center in E. coli ribosomes, and (iii) Um-Gm-omega, the most densely modified sequence in eukaryotic 26 S rRNA, is universally conserved at a fixed site in the putative peptidyl transferase center of all eukaryotic ribosomes.