The 5' cap (m7GpppN) and the poly(A) tail of eukaryotic mRNAs work in concert to establish an efficient level of translation in vivo. Nevertheless, several mRNAs naturally lack a cap or a poly(A) tail. Determining how these messages effectively compete for the translational machinery not only reveals alternative mechanisms for translational competence, but can also underscore similarities between alternative mechanisms and the standard cap/poly(A) tail interaction. The genomic RNA of tobacco etch virus (TEV), a potyvirus, is a polyadenylated mRNA that naturally lacks a cap (m7GpppN) at the 5'-terminus and yet is a highly competitive mRNA during translation. The 144-nt 5'-leader is largely responsible for directing efficient translation and can greatly increase the translational competence of reporter mRNAs. We have examined the synergy between the TEV 5'-leader and the poly(A) tail in transfected plant and animal cells. The TEV 5'-leader functioned optimally as a regulator of reporter mRNA translation only when a poly(A) tail was present. The effect of the TEV 5'-leader on the translation of capped transcripts was significantly less than that for uncapped mRNAs, suggesting that the TEV 5'-leader and the cap may promote similar steps in translation.