SEVERAL model systems have been used to evaluate the alpha-helical propensities of different amino acids(1-7). In contrast, experimental quantitation of beta-sheet preferences has been addressed in only one model system, a zinc-finger peptide(8). Here we measure the relative propensity for beta-sheet formation of the twenty naturally occurring amino acids in a variant of the small, monomeric, beta-sheet-rich, IgG-binding domain from protein G. Amino-acid substitutions were made at a guest site on the solvent-exposed surface of the beta-sheet. Several criteria were used to establish that the mutations did not cause significant structural changes : binding to the Fc domain of IgG, calorimetric unfolding and NMR spectroscopy. Characterization of the thermal stabilities of these proteins leads to a thermodynamic scale for beta-sheet propensities that spans a range of similar to 2 kcal mol(-1) for the naturally occurring amino acids, excluding proline. The magnitude of the differences suggests that beta-sheet preferences can be important determinants of protein stability.