Background: The serum bactericidal test measures the highest level of an antibiotic-containing serum dilution at which 99.9% of bacteria are killed. In this study the serum bactericidal activity of piperacillin/tazobactam was determined for bacteria often involved in severe infections. In earlier studies titres ≥1:8 in the serum bactericidal tests correlated well with clinical success in the treatment of endocarditis and osteomyelitis as well as bacterial eradication. Methods: Blood samples of 6 healthy volunteers were taken before and 1 and 4 h after piperacillin/tazobactam (4.5 g) administration. Serum concentrations and serum bactericidal activity were determined for 10 strains each of Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, both piperacillin-resistant and piperacillin-susceptible according to NCCLS guidelines. Results: 100% of S. aureus and piperacillin-susceptible E. coli, 90% of piperacillin-resistant E. coli and 80% of P. aeruginosa were killed 1 h after drug administration. 4 h after drug administration serum bactericidal activity decreased to 60% for S. aureus, 90% for piperacillin-susceptible E. coli, 80% for piperacillin-resistant E. coli and 30% for P. aeruginosa. Conclusions: Excellent serum bactericidal activity of piperacillin/tazobactam was recorded 1 h after drug administration for S. aureus, E. coli and P. aeruginosa. After 4 h limited killing rates for P. aeruginosa could be detected, which supports the idea of a combination therapy. Copyright © 2004 S. Karger AG, Basel.