Beta-amyloid peptide (A beta) is the major protein constituent found in senile plaques in Alzheimer's disease (AD). It is believed that A beta plays a role in neurodegeneration associated with AD and that its toxicity is related to its structure or aggregation state. In this study, an approach based on chemical modification of primary amines and mass spectrometric (MS) detection was used to identify residues on A peptide that were exposed or buried upon changes in peptide structure associated with aggregation. Results indicate that the N terminus was the most accessible primary amine in the fibril, followed by lysine 28, then lysine 16. A kinetic analysis of the data was then performed to quantify differences in accessibility between these modification sites. We estimated apparent equilibrium unfolding constants for each modified site of the peptide, and determined that the unfolding constant for the N terminus was approximately 100 times greater than that for K28, which was about six times greater than that for K16. Understanding A beta peptide structure at the residue level is a first step in designing novel therapies for prevention of A beta structural transitions and/or cell interactions associated with neurotoxicity in Alzheimer's disease.