The lens fiber cell cytoskeleton includes a protein with a relative molecular weight, by SDS PAGE, of 115 kD. This protein has been purported to be, or be related to alpha-actinin, a highly-conserved family of actin-binding cytoskeletal proteins common to many tissues across a wide phylogenetic range. In this report we assess the relationship between the 115 kd lens fiber cell protein and alpha-actinin. Assessment of relative molecular weight, immunologic cross-reactivity, and partial sequence analysis suggest that the 115 kD lens fiber cell cytoskeletal protein and alpha-actinin are either unrelated, or, at best, that the lens protein represents an unusually divergent isoform of the alphaactin family of proteins. Immunochemical analysis of homogenates of bovine heart and red blood cells indicate that these tissues express a protein which is weakly cross-reactive with the lens 115 kD protein, but that this cross-reactive protein is not alpha-actinin.