This study compared the BACTEC blood culture system (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md) with conventional culture methods for recovery and time to detection of significant isolates from normally sterile body fluids. A total of 412 specimens were included in the study. Half of the specimens were inoculated directly into the automated blood culture system. The remaining specimens were centrifuged at 3000 rpm for 10 min and were inoculated onto conventional media. Clinically significant microorganisms were isolated from 41 specimens (10%) by both culture systems; however, for 62 specimens (14.9%), growth was detected only with the BACTEC system. No isolates were detected with only conventional culture methods. A significant difference was noted between the blood culture system and routine culture methods for recovery of pathogenic microorganisms that were from sterile body fluids. The most frequently isolated microorganisms recovered only with the blood culture system were gram-positive cocci; gram-negative bacilli were the most frequently isolated microorganisms that were recovered with both culture methods. Streptococcus pneumoniae, Streptococcus viridans, Aeromonas hydrophila, and Brucella were recovered only with the blood culture system. Furthermore, the mean time to detection of significant pathogens was significantly less with the blood culture system than with conventional media. The BACTEC blood culture system was found to improve the yield of clinically significant isolates from normally sterile body fluids with reduced time to detection; it may be advantageous for isolation of fastidious microorganisms, such as Brucella and S pneumoniae, especially from cerebrospinal and synovial fluid specimens.