Eighteen evaluable children with recurrent Langerhans' cell histiocytosis (LCH) which was resistant to standard therapy, were treated with etoposide (VP 16-213), 200 mg/m2/day for 3 days every 3 weeks, to study the efficacy and toxicity of this drug. Complete and partial responses were demonstrated in 15 patients (83.3%). Only one of the 12 children achieving a complete remission has relapsed. No dose-limiting major toxicities were registered. Although etoposide might be an effective treatment in recurrent LCH which needs a chemotherapeutic approach, it is emphasized that this drug must be used carefully.