Patients at two tertiary-care medical centers were evaluated to determine the clinical significance of anaerobic isolates from their blood specimens and to identify whether aerobic and/or anaerobic conditions were necessary for the detection of Streptococcus pneumoniae isolates. Significant anaerobes were isolated from only 0.1% and 0.4% of all blood cultures collected. The majority of patients with significant anaerobes had clinical conditions in which anaerobes are known to cause infections. Of the S. pneumoniae organisms, 83% were isolated only from the aerobic bottles of a blood culture set. These data lend support to the recommendations for the selective ordering of anaerobic blood cultures without compromising the isolation of S. pneumoniae.