αA peptide forms with age in the lens nucleus of humans and guinea pigs， and binds to αA-crystallin by hydrophobic bonds to produce protein aggregates. The purpose of the present study was to use negative-stain transmission electron microscopy (TEM) to investigate peptide/crystallin structures that form when αA peptide is incubated with recombinant human (HU) and guinea pig (GP) αA-crystallin， and GP αA-crystallin， under physiological conditions of temperature and pH. HU and GP αA-crystallin each consists of 173 amino acid residues with only eight differences. GP αA-crystallin contains an insertion of 23 amino acids into the sequence for normal GP αA-crystallin. Synthetic αA peptide was incubated with each crystallin for 24?h in phosphate buffered saline at 37 C， pH 7.4. Samples were loaded onto electron microscopy grids and analyzed by TEM. With GP αA-crystallin， the αA peptide appeared to first form up to 700?nm long， independent peptide fibrils， which subsequently bound numerous αA-crystallin oligomers along the entire length of the fibril to form up to 30?nm thick peptide/oligomer fibril structures. In contrast， HU αA-crystallin somehow prevented independent αA peptide fibrillation， and instead joined with the peptides to form amorphous aggregates and linear chains of αA oligomers. When incubated alone， GP αA-crystallin eventually lost all oligomeric structure and formed amorphous aggregates. However， addition of αA peptide to the incubation medium resulted in the formation of highly-organized peptide/αA oligomer amyloid fibrils， nearly 400?nm in length， with oligomer dimers appearing to stack one on top of another. Mature peptide/αA oligomer fibrils were highly compressed and 40% thicker than observed protofibrils (17?nm vs. 12?nm thickness). Use of a control V72P αA-crystallin peptide， as well as addition of the disulfide bond reducing agent DTT to the incubation medium， prevented fibril formation. Turbidity and Thioflavin T fluorescence analyses confirmed the observed peptide-induced fibril formation. This study represents the first time that fibrillation of αA-crystallin has been accomplished under physiological conditions of temperature and pH without use of denaturants. Fibrillation of GP αA-crystallin was linked with possible intermolecular disulfide-crosslinking of oligomers. The finding that αA peptide induces aggregate formation with HU αA-crystallin supports a role for this peptide in the development of HU nuclear cataract.