The use of vancomycin has increased dramatically in recent years with the emergence of methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococci as important hospital pathogens. A patient receiving vancomycin 1.75 g intravenously as a single daily dose developed a syndrome characterized by high fever, erythema multiforme, eosinophilia, and presumed interstitial nephritis. This delayed hypersensitivity reaction resolved with discontinuation of the drug and treatment with methylprednisolone.