Mesna (sodium-2-mercaptoethansulfonate) is used in the prophylaxis of cyclophosphamide (CYC)-induced hemorrhagic cystitis. Four patients being treated with "low dose" CYC and prednisone for vasculitis developed severe side effects to Mesna. Fever, arthralgia, myalgia, tachycardia, electrocardiogram changes consistent with perimyocarditis, erythroderma, bullous skin and mucous membrane lesions, and abdominal complaints with profuse diarrhea were noted approximately 3 weeks after the initiation of therapy for CYC-induced leukopenia and a conservatively reduced prednisone dosage. Positive reexposure tests confirmed the association to Mesna use, and hypersensitivity skin tests demonstrated a delayed hypersensitivity reaction.