In this evaluation of the prevalence and quality of systemic antibiotic use in nursing homes, 42 skilled nursing facilities (SNFs) and their 11 attached intermediate care facilities (ICFs) were surveyed. A random sample of 2238 patients (51%) from the total of 4378 beds was selected and of these, 7.7% of the total (8.6% of the SNF and 4.5% of the ICF) patients were on systemic antibiotics on the day of the survey. The most common suspected sites of infection were urinary tract (58.4%), lower respiratory tract (19.1%), and skin or subcutaneous tissue (4.6%). Criteria for appropriateness of initiating systemic antibiotics, for adequacy of initial diagnostic workup, and for appropriate specific antibiotics were developed by the authors, with input from a group of medical directors of nursing homes, based on Centers for Disease Control and Federal Drug Administration guidelines. Evidence to start an antibiotic was judged adequate in 62.4% of cases. Workups were considered inadequate in a high proportion of cases. For example, urinalysis was ordered in only 23.8% and urine culture in 57.4% of suspected urinary tract infections; chest x-ray was ordered in 24.2% and sputum culture in 3.0% of suspected lower respiratory infections. Recommendations are made as to minimum adequate workup for suspected infections and appropriate evidence to justify start of a systemic antibiotic, recognizing the limitations in diagnostic modalities in the nursing home setting and the special problems of their resident populations.