In a bilaterally paired double-blind comparison study, a cream containing 0.1% 13-cis-retinoic acid (13-cis-RA) and cream base only were applied over 4 weeks in seven patients with non-erythrodermic lamellar ichthyosis (NELI), two patients with Darier's disease and one patient with autosomal dominant ichthyosis vulgaris (ADIV). In two patients with NELI and two patients with Darier's disease a half-side effect was observed in favour of the side treated with 13-cis-RA. In three patients an induction of cytokeratin-4, and in one of these patients expression of cytokeratin-13, were observed after therapy. Topical 13-cis-RA appears to be a promising approach in the treatment of disorders of keratinization. The selective modulation of the cytokeratin pattern may provide an immunohistochemical tool to investigate the mode of action of retinoids.