ζ-Crystallin is a major component of the water-soluble proteins of the guinea pig lens. We have constructed a lens cDNA library from one- to seven-day-old guinea pigs in the plasmid Bluescript KS + and used the 16 amino acid (aa) sequence of a CNBr peptide to design an oligodeoxyribonucleotide probe. Analysis of two positive clones and direct sequence of the 5′ end of the RNA resulted in the completion of a most probably full-length mRNA comprising 1842 nucleotides (nt). The ATG start codon occurs 83 nt downstream from the 5′ end. The open reading frame, ending with a stop codon at nt position 1070, predicts a protein of 328 aa with a calculated M r of 35071. Comparison of the amino acid sequence with the National Biomedical Research Foundation protein data base reveals a significant similarity of ζ-crystallin with the enzyme of the alcohol dehydrogenase family.