The UPL (Upjohn Pharmaceutical Limited) rat is a dominant hereditary cataract model that develops early-onset cataracts (E-type) in rats homozygous for the trait, and late-onset cataracts (L-type) in heterozygous rats. Using antibodies specific to the calpain-proteolyzed forms of alpha-crystallin, we determined their immunohistochemical localization of the L- and E-rat lenses. Immunoreactivity indicating the proteolyzed forms was detected and found restricted to degenerated lens fibers of the mature stage of the L-rat cataract. Lenses from E-rats, which have abnormally elongated lens fibers during the fetal period, had proteolyzed alpha-crystallin forms at 1 week of age. The results of this present study indicate that calpain-mediated proteolysis of alpha-crystallin occurred in the UPL rat lenses during cataract formation and that calpain may be an important factor in the development of complete lens opacification.