To study the regulation of hair differentiation, a murine genomic clone, gUHS-SER-M16, was isolated that contained two members of the family of serine-rich ultra high sulfur protein genes. One of the genes, gUHS-SER-1, encodes 230 amino acids with 40% cysteine and 23% serine; the other gene, gUHS-SER-2, encodes 223 amino acids with 41% cysteine and 21% serine. The similarity between the two genes is 73%, and both have several 10-amino acid repeats within their coding regions. In the prospective promoter region, there are several regions of similarity including a "TATA" box, with neither gene having a "CAT" box. At the 3' untranslated region, there is no similarity, and thus a fragment from this region was used as a hybridization probe for RNA dot-blots and for in situ hybridizations. The RNA dot-blot showed elevated levels of mRNA during the active phases of hair growth and low levels during the resting phases. In situ hybridizations show that mRNA for the ultra high sulfur protein gene is found during the active phases of the hair cycle not only in the medulla and the inner root sheath of the forming hair but also in upper layers of the epidermis of skin.