While all codons that specify amino acids are universally recognized by tRNA molecules, codons signaling termination of translation are recognized by proteins known as class-I release factors (RF). In most eukaryotes and archaea a single RF accomplishes termination at all three stop codons. In most bacteria, there are two RFs with overlapping specificity, RF1 recognizes UA(A/G) and RF2 recognizes U(A/G)A. THE HYPOTHESIS: First, we hypothesize that orthologues of the E. coli K12 pseudogene prfH encode a third class-I RF that we designate RFH. Second, it is likely that RFH responds to signals other than conventional stop codons. Supporting evidence comes from the following facts: (i) A number of bacterial genomes contain prfH orthologues with no discernable interruptions in their ORFs. (ii) RFH shares strong sequence similarity with other class-I bacterial RFs. (iii) RFH contains a highly conserved GGQ motif associated with peptidyl hydrolysis activity (iv) residues located in the areas supposedly interacting with mRNA and the ribosomal decoding center are highly conserved in RFH, but different from other RFs. RFH lacks the functional, but non-essential domain 1. Yet, RFH-encoding genes are invariably accompanied by a highly conserved gene of unknown function, which is absent in genomes that lack a gene for RFH. The accompanying gene is always located upstream of the RFH gene and with the same orientation. The proximity of the 3' end of the former with the 5' end of the RFH gene makes it likely that their expression is co-regulated via translational coupling. In summary, RFH has the characteristics expected for a class-I RF, but likely with different specificity than RF1 and RF2.