A 48-year-old man, hospitalized after experiencing subarachnoid hemorrhage secondary to a basilar aneurysm, received vancomycin for methicillin-resistant Staphylococcus aureus sepsis. He developed neutropenia 16 days after the start of vancomycin therapy, and his white blood cell count decreased to a nadir of 1200 cells/mm3. Vancomycin was discontinued, and granulocyte-colony stimulating factor (G-CSF) therapy was begun. The patient was rechallenged with a single dose of vancomycin 1 g in preparation for intraarterial aneurysm coiling. His white blood cell count dropped to 600 cells/mm3 but returned to normal with continued G-CSF therapy. A diagnosis of vancomycin-induced neutropenia was considered. Subsequent testing by granulocyte agglutination and granulocyte immunofluorescence assays revealed that his serum was positive for an antigranulocyte antibody. A test for HLA antibody reactivity was negative. Monoclonal antibody immobilization of granulocyte antigens assay failed to determine the antigen specificity of his granulocyte antibody.