Crystallins of the normal eye lens have a specific structure that maintains lens transparency. This structure reportedly arises from a short-range order. The age-related post-translational changes and high molecular weight (HMW) aggregation disrupt the normal structure and decrease lens transparency. In the current study, we have carried out fluorescence measurements (polarization and extrinsic probe binding) in an attempt to understand protein interaction and aggregation. Based on polarization measurements of dansyl chloride (DCl) labeled gamma-crystallin, there is a hetero-interaction among crystallins (alpha-gamma, beta-gamma, etc.) but no self-interaction in gamma-crystallin (gamma-gamma) (less than 30 mg ml-1). Alpha-crystallin is rich in hydrophobic region and possibly has a self-interaction through hydrophobic interaction. Hydrophobic probes, ANS (1-anilinonaphthalene-8-sulfonic acid) and DPH (1,6-diphenyl 1,3,5-hexatriene) measurements show that alpha-crystallin is a very hydrophobic protein. HMW alpha-crystallin appears to be even more hydrophobic, indicating that the post-translational unfolding exposes more hydrophobic groups which facilitate HMW aggregation. The HMW aggregation results from highly hydrophobic proteins which tend to become thermodynamically more stable.