The development of granulocytopenia during oxacillin therapy is reported in 2 patients. In both cases the onset of granulocytopenia occurred 24 days after therapy was instituted with similar clinical presentations. The bone marrow aspirates revealed myeloid hyperplasia, left shift and maturation arrest. 24 h after oxacillin was discontinued the granulocyte counts rapidly rose towards normal, with subsequent complete recovery. Although sought for, leukoagglutinins could not be demonstrated in either patient. The occurrence of granulocytopenia in patients receiving natural and semisynthetic penicillins is reviewed and the mechanisms are outlined.