We report a case of acute encephalopathy in a patient with Crohn's disease who had taken sulfasalazine for 1 month. The development of a toxic hepatitis and dermatitis prompted interruption of the drug. Four days later, neurological symptoms became evident. These included acute monoparesis of the left arm, the development of stupor and coma, with endorotation of both arms and a left Babinski sign. CT and magnetic resonance imaging revealed multiple lesions in the white and gray brain matter, suggesting diffuse cerebral microangiitis. All cerebrospinal fluid examinations were negative. Methylprednisolone was given intravenously. Complete clinical normalization followed. Neurotoxicity secondary to sulfasalazine has seldom been reported in the literature. We found certain similarities between this case and two previous case reports suggesting a hypersensitivity reaction to sulfasalazine or one of its metabolites. For ethical reasons, no rechallenge was performed.