We have investigated how structure-dependent mutation matrices derived in previous work correlate with various physical-chemical properties of the 20 naturally occurring amino acids. Among the properties we investigated were delta G of transfer from water to octanol and cyclohexane, alpha helical and beta sheet propensity, size, and charge. We found that the delta G of transfer to octanol had a high correlation with matrices for all categories of residues, especially the matrices for buried and exposed positions. This result suggests that octanol is a good model for understanding both the changes in stability resulting from substitutions of buried residues and changes in foldability resulting from varying exposed residues. We also found the correlations of the matrices with size and charge varied with the local environment, and that neither alpha helical nor beta sheet propensity had high correlations with most matrices. Thus, conservation of size and charge appear to be important in specific environments, and conservation of alpha helix and beta sheet propensity do not seem to be key factors.