There are frequent contacts between aromatic rings and sulfur atoms in proteins. However, it is unclear to what degree this putative interaction is stabilizing and what the nature of the interaction is. We have investigated the aryl-sulfur interaction by placing a methionine residue diagonal to an aromatic ring on the same face of a beta-hairpin, which places the methionine side chain in close proximity to the aryl side chain. The methionine (Met)-aryl interaction was compared with an equivalent hydrophobic and cation-pi interaction in the context of the beta-hairpin. The interaction between phenylalanine (Phe), tryptophan (Trp), or cyclohexylalanine (Cha) and Met stabilized the beta-hairpin by -0.3 to -0.5 kcal mole(-1), as determined by double-mutant cycles. The peptides were subjected to thermal denaturations that suggest a hydrophobic driving force for the interactions between Met and Trp or Cha. The observed interaction of Met or norleucine (Nle) with Trp or Cha are quite similar, implying a hydrophobic driving force for the Met-pi interaction. However, the thermodynamic data suggest that there may be some differences between the interaction of Met with Trp and Phe and that there may be a small thermodynamic component to the Met...Phe interaction.