A patient receiving vancomycin for a serious staphylococcal infection had a lupus-like syndrome characterized by a malar rash, pain and erythema of the cartilage of both ears, and tender erythematous and hemorrhagic lesions of the finger tips. Biopsy and direct immunofluorescence study of the skin showed changes consistent with the diagnosis of lupus erythematosus. The possible development of a drug-induced vasculitis or lupus-like syndrome should be added to the list of rare toxic effects of vancomycin.