To study the regulation of the hair cycle in the mouse, we have isolated and characterized a gene for ultra high sulfur keratin that is expressed specifically during the active hair growth cycle. The gene (gUHSK-704Eco) was isolated as a member of a gene cluster on a recombinant phage with a DNA insert of 18 kb that was isolated by screening a murine genomic library at low stringency with a synthetic oligonucleotide derived from a sheep high sulfur keratin gene (Powell, Res. 1983 11, 5327). The murine ultra-high sulfur keratin gene has no intervening sequence; the 558 nucleotide of the coding region specify 186 amino acids, of which 70 (37%) are cysteine. A Cys-Cys-Gln-Pro repeat is found 12 times within the coding region. RNA dot blots show that the ultra-high sulfur keratin gene is expressed during the hair cycle concomitant with the anterior-posterior temporal pattern of the normal murine hair cycle.