Twenty patients with disabling disorders of keratinization were treated with Tigason (etretinate, Ro 10-9359), an oral aromatic retinoid, and the clinical responses and the effects on the skin were monitored. Most patients showed a considerable clinical improvement within 4 weeks. Side effects, such as cheilitis, were common but mostly transient or minor. In the skin there was a decrease in glucose-6-phosphate dehydrogenase activity within the granular cell layer of the epidermis, and an increase in mean epidermal thickness and mean corneocyte area. However, there was little apparent effect on epidermal proliferation or on histological and ultrastructural appearances. These findings suggest that the drug acts at a late stage of epidermal differentiation.