A young patient with Netherton's syndrome characterized by the classic triad of ichthyosis linearis circumflexa, trichorhexis invaginata and atopy was treated with Acitretin, a new retinoid preparation: 35 mg Acitretin/day resulted in a severe, erosive dermatitis which necessitated interruption of therapy. Even with 10 mg/day the patient had intolerable irritation of the integument. After a further dosage reduction to 5 mg/day there were no obvious side effects and a long-term treatment was possible, resulting in an obvious reduction of the ichthyotic lesions and improved hair growth. Electron microscopy in the active part of the skin lesions from untreated skin revealed granular, membrane-enclosed material intracellularly and in the intercellular spaces of the granular layer. Keratinization was almost completely suppressed. Therapy with Acitretin drastically reduced the deposition of intra- and extracellular material and normalized keratinization. Our results underline the importance of starting retinoid therapy in Netherton's syndrome at a low dosage and adjusting it carefully in each case with reference to the skin manifestations and the side effects.