A 32-year-old Japanese woman, who had a treatment history of systemic lupus erythematosus (SLE) with lupus nephritis World Health Organization class IV for 11 months, visited our hospital due to fever, facial erythema, and erosion of the oral cavity on November 10, 2003. Her mucosal erosion and facial skin erythema progressed over the following week, and Stevens-Johnson syndrome was diagnosed due to pathological findings of the skin. Among the administrated drugs, only mizoribine, started 6 months earlier, produced a positive reaction in the drug lymphocyte stimulation test. Increased prednisolone and high dose intravenous gamma-globulin were given successfully. Cyclosporine at 50 mg was administered to control the SLE, followed by an increase to 100 mg on January 7, 2004. She suffered from abdominal pain, blindness, and convulsion on January 9. The magnetic resonance image of her brain prompted a diagnosis of reversible posterior leukoencephalopathy syndrome. After withdrawal of cyclosporine and control of hypertension, symptoms disappeared rapidly. Cyclophosphamide pulse therapy was successfully administrated to control lupus nephritis. This is the first report describing the relationship between Stevens-Johnson syndrome and mizoribine. Although the use of mizoribine is thought to be safe, careful observation is necessary.