The heterogeneity inherent among gamma-crystallins of the mouse lens was investigated by sequence analysis of three gamma-crystallin-specific cDNAs. Comparison of the nucleotide sequence of these cDNAs and one previously reported by us revealed that the four gamma-cDNAs share 80-90% homology in nucleotide sequence. The entire 3' half of the coding region shows more variability than the 5' half, whereas the greatest variability is observed in the 3' untranslated region where numerous base substitutions, deletions, and insertions seem to have occurred. Alignment of the amino acid sequences of the four mouse gamma-crystallins according to the known four structural motifs of the major calf gamma-crystallin, gamma-II, suggests that all four mouse polypeptides are structurally very similar to calf gamma-II. However, most of the mouse polypeptides differ from gamma-II by the absence of one amino acid residue, resulting in a shorter connecting peptide between the two globular domains of the protein. Primary sequence alignment also revealed that the four mouse gamma-crystallins are most divergent in the third structural motif of the polypeptide. The significance of these differences in terms of the structure and function of the gamma-crystallins in the mouse lens is discussed.