To determine the clinical significance and therapeutic impact of pediatric blood cultures, we analyzed 1650 cultures comparing conventional broth and direct plating methods. The rate of positive cultures was 5.8%. Of 96 positive cultures 68 were deemed clinically significant. The mean time to detection was 23.8 and 33.7 hours, and the sensitivity was 89 and 83% in the Isolator and broth systems, respectively. The overall rate of insignificant isolates was 1.7% and was similar for both methods. Clinical interventions based on blood culture results occurred in 39 patients, primarily those with pneumococcal and staphylococcal bacteremia. Only six of 28 clinically insignificant isolates had negative impact. Use of the pediatric Isolator permitted earlier institution of appropriate therapies and shorter duration of unneeded or toxic therapies without frequent negative impact. Since direct costs were comparable the Isolator system may be a clinically valuable and cost effective alternative to conventional methodology.