A case of severe sulfasalazine-induced hepatotoxicity is reported in a 14-year-old girl with Crohn's disease. Fourteen days after beginning sulfasalazine, she developed a systemic reaction characterized by high fever, maculopapular rash, lymphadenopathy, abdominal pain, and malaise, with tender hepatomegaly and elevated liver functions, leukemoid reaction, with eosinophilia, and immune complexes. She responded promptly to high-dose intravenous steroids with complete recovery. This case was compared to the three similar pediatric cases in the literature. The latent period was 11-19 days between sulfasalazine therapy and the onset of high fever, generalized lymphadenopathy, and pruritic maculopapular rash that spared palms and soles and resolved with desquamation. All children had hepatotoxicity indicated by tender hepatomegaly, elevated liver enzymes, and histologic inflammation on liver biopsy. The similarity between these features and those of other sulfa-induced hepatotoxic reactions suggests that the sulfapyridine moiety is the etiologic agent in these hypersensitivity reactions. Those children with circulating immune complexes responded well to steroids. Proper therapy for this rare but severe idiosyncratic reaction includes prompt recognition and discontinuation of sulfasalazine, and high-dose corticosteroid therapy.