In this paper, we reported a novel monoclonal antibody against human keratins, R 6-2-14. The antigen used for immunization was derived from human callus, keratins in which traditionally are classified as "Soft" keratins. However, when we studied the tissue specificity of this antibody, it was found that it only reacted strongly with "Hard" keratins of various mammalian species, but no detectable cross-reactivity with any of the "Soft" keratins. This antibody may provide a useful tool for the study of hair regeneration, nail regeneration, corn pathology and differentiation of mammalian epidermal derivatives.