The propensity of an amino acid to form an α helix in a protein was determined by multiple amino substitutions at positions 44 and 131 in T4 lysozyme. These positions are solvent-exposed sites within the α helices that comprise, respectively, residues 39 to 50 and 126 to 134. Except for two acidic substitutions that may be involved in salt bridges, the changes in stability at the two sites agree well. The stability values also agree with those observed for corresponding amino acid substitutions in some model peptides. Thus, helix propensity values derived from model peptides can be applicable to proteins. Among the 20 naturally occurring amino acids, proline, glycine, and alanine each have a structurally unique feature that helps to explain their low or high helix propensities. For the remaining 17 amino acids, it appears that the side chain hydrophobic surface buried against the side of the helix contributes substantially to α helix propensity.