The Difco ESP and Organon Teknika BacT/Alert (BTA) systems were evaluated in a clinical study of 5,421 aerobic and 5,035 anaerobic blood cultures. Of 405 clinically significant positive cultures evaluated, 272 grew in both systems, 86 grew in ESP only, and 47 grew in BTA only (P < 0.005). Of 320 organisms detected in aerobic bottles, 208 grew in both systems, 68 grew in ESP only and 45 grew in BTA only (P < 0.05), with Staphylococcus aureus the only organism showing a statistically significant difference. The ESP anaerobic bottle also detected more anaerobes (16 of 17 versus 4 of 17, P < 0.005) and more organisms overall (57 versus 34, P < 0.05). However, with the exception of patients with anaerobic bacteremia (12 of 13 for ESP and 4 of 13 for BTA, P < 0.05), there was no statistical difference in the detection of patient episodes. Average detection time of matched aerobic bottles was 18.3 h for ESP and 22.0 h for BTA (P < 0.001). For matched pairs of anaerobic bottles, the average detection time was faster in the BTA bottles (P < 0.001), because of the growth of facultative organisms. To explore the differences in anaerobic detection more fully, 20 sets of anaerobic bottles were seeded with 12 anaerobic species mixed with human blood. ESP grew more organisms (17 of 20 versus 10 of 20, P < 0.025), and the average time to detection for the 10 paired positive cultures was 21.6 h for ESP and 50.8 h for BTA (P < 0.05). Times for loading and unloading bottles were similar for both systems.