Fluorescence Resonance Energy Transfer (FRET) was used to study protein structures within soluble oligomer intermediates of amyloid and non-amyloid aggregates. Three protein aggregation systems were studied using fluorescence donor and acceptor near the N and C terminus:(1) Alzheimer's Ab 1-40 peptide.(2) 20-residue polyglutamine K 2 Q 16 K 2 .(3) 20-residue polyglutamic acid E 20 . (non-amyloid) The aggregation of each peptide showed different conformational changes: Ab 1-40 partially compacted into a structure consistent with solid-state NMR structures, K 2 Q 16 K 2 extended to form b-sheets, and E 20 compacted heavily into b-hairpins. However, based on donor-acceptor distances, soluble oligomers conformations of all three peptides show a remarkable degree of similarity to their monomeric precursors, albeit with a slightly expanded conformation for Ab 1-40 and E 20 . These findings support assembly models of small soluble oligomers which largely consist of monomer-like structures, with some increase in a-helical content for Ab 1-40 . These donor-acceptor distances are used to directly assess the accuracy of different molecular dynamics force fields in the study of these soluble oligomers.