The contributions of interstrand side chain-side chain contacts to ss -sheet stability have been examined with an autonomously folding ss -hairpin model system. RYVEV(D)PGOKILQ-NH2 (P-D = D-proline, O = ornithine) has previously been shown to adopt a ss -hairpin conformation in aqueous solution, with a two-residue loop at D-Pro-Gly. In the present study, side chains that display interstrand NOEs (Tyr-2, Lys-9, and Leu-11) are mutated to alanine or serine, and the conformational impact of the mutations is assessed. In the ss -hairpin conformation Tyr-2 and Leu-11 are directly across from one another (non-hydrogen bonded pair). This "lateral" juxtaposition of two hydrophobic side chains appears to contribute to ss -hairpin conformational stability, which is consistent with results from other ss -sheet model studies and with statistical analyses of interstrand residue contacts in protein crystal structures. Interaction between the side chains of Tyr-2 and Lys-9 also stabilizes the 6-hairpin conformation. Tyr-2/Lys-9 is a "diagonal" interstrand juxtaposition because these residues are not directly across from one another in terms of the hydrogen bonding registry between the strands. This diagonal interaction arises from the right-handed twist that is commonly observed among ss -sheets. Evidence of diagonal side chain-side chain contacts has been observed in other autonomously folding ss -sheet model systems, but we are not aware of other efforts to determine whether a diagonal interaction contributes to beta -sheet stability.