Lens proteins from the guinea pig (Cavia porcellus) were found to be similar to those of other mammals with the exception of the presence of a previously undescribed constituent comprising about 10% of the total soluble lens proteins. This oligomeric protein is composed of polypeptides with apparent molecular weight of 38,000 and elutes from gel exclusion chromatography columns in the BH-crystallin fraction. Following purification by ion exchange chromatography an antibody was raised against the protein. Using that antibody and antibodies specific for other crystallins we could detect no cross-reactivity between the guinea pig protein and any other reported lens cystallin. This protein, which we have named zeta (ζ)-crystallin, is the first reported mammalian lens crystallin which is not part of theα−orβ-γfamilies of crystallins. Unlike all other known mammalian crystallins, which have little or no a-helical structure, zeta-crystallin is estimated to be approximately 30–40%α-helix.