The fibrous proteins of the malpighian layer of human epidermis (prekeratin) have been isolated with citrate buffer, pH 2.65, and shown to consist of 7 polypeptide chains varying in molecular weight from 45,000 daltons to 67,000. Some variation in the number and amount of the components was observed in prekeratin prepared from the epidermis of different individuals. The fibrous proteins of the stratum corneum were isolated with Tris buffer, pH 9.0, containing 6 M urea and 0.1 M mercapto-ethanol and were found to have a pattern similar to prekeratin but not identical to it. However, fibrous protein isolated from the superficial layers of the stratum showed a considerably different pattern indicating that there was post-translational modification of the protein in the late stages of keratinization. These data show that human keratin has the same heterogeneity which was observed previously in cow epidermis. This was further confirmed by studying the polypeptide chain content of prekeratin from a large number of lesions showing benign epidermal hyperplasia, where considerable variation in composition was observed.