Assembly of proteins and peptides into amyloid fibrils is characteristic of the pathology of a number of degenerative diseases, of which perhaps the best known is Alzheimer's. Neuronal death in Alzheimer's disease has been linked to aggregation of P-amyloid peptide and deposition of the aggregates in brain tissue. Recent studies suggest that soluble intermediate oligomers rather than fully formed fibrils may be responsible for P-amyloid's toxicity; consistent with this hypothesis, some compounds that inhibited P-amyloid toxicity were found to accelerate aggregation of the peptide. The degree of increase of aggregation caused by these compounds was shown to correlate strongly with their effect on the surface tension of aqueous buffers (Gibson, T. J.; Murphy, R. M. Biochemistry 2005, 44, 8898-8907). In work reported here, we used group contribution methods to calculate infinite dilution activity coefficients of moieties contained in these compounds. We demonstrate that activity coefficients calculated in this manner are strongly predictive of effects of these peptides on solvent surface tension and on P-amyloid aggregation. These results suggest that group contribution calculations can be used for a priori design of compounds that modulate aggregation of peptides through their effect on solvent properties.