Alignment of the internal ribosome entry sites (IRES) of members of the Enteroviridae-Rhinoviridae (E/R) family reveals a consensus loop sequence of AANCCA closed by a C.G base pair. The consensus sequence was present in two distinct loops in domains III and VI. Four hairpins corresponding to the most common loop sequences, AAUCCA, AAACCA, GAACCA and AUCCA, were synthesized and studied by UV spectroscopy. Although all four oligomers had similar UV melting points their thermodynamic parameters revealed differing stabilities consistent with their loop size. Comparison of the aromatic proton and H1' chemical shifts for the four loop sequences obtained from this and our previous NMR study revealed strikingly similar trends. The pattern of chemical shifts suggest similar solution structures in spite of differences in sequence and loop size. This common structure provides a structural basis for their sequence conservation in E/R IRESes.