Experimental nuclear cataract produced by an overdose of sodium selenite exhibited limited proteolysis, including breakdown of main intrinsic polypeptide (MIP26) to 24 and 22 kD fragments (1). Micro-sequencing and site specific immunologic probes were used in the present study to determine regions of cleavage in MIP26 during selenite cataractogenesis. Data suggested that proteolysis occurred in the C-terminus of MIP26. This may have lead to exposure of normally hidden amino acid residues on the C-terminal extension of MIP26. Loss of antigenicity of the N-terminus occurred. These significant changes to the MIP26 molecule might adversely affect communication between lens fiber cells and contribute to selenite cataract.