This study describes a family of 30 people in which 14 members have hereditary epidermolytic palmoplantar keratoderma. Four patients were treated with an oral aromatic retinoid for up to 5 months. They responded in a uniform and dramatic way: 10-14 days after the onset of therapy, the hyperkeratotic horny layer was sequestered in large sheets resulting in normal appearing skin and restoration of normal surface sensitivity. Biopsies revealed that the underlying disorder of keratinization had remained unchanged. Treatment with the retinoid had to be discontinued as the sensitivity and vulnerability restricted normal function of hands and feet.