OBJECTIVE: To investigate the production of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) induced by live Gram-negative and Gram-positive bacteria in whole blood in vitro. METHODS: In all, 49 different isolates were studied. Each of the 49 different isolates was incubated for 4 h with whole blood at a ratio of one monocyte per 1--5 bacteria. Plasma was then separated and frozen, and the concentrations of TNF-alpha and IL-6 were measured by enzyme immunoassays. RESULTS: There was a positive correlation between TNF-alpha and IL-6 values, r=0.9. Gram-negative bacteria induced higher levels of both TNF-alpha and IL-6 than Gram-positive bacteria. Group G streptococci (GGS) induced higher levels of TNF-alpha than Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis and group A streptococci (GAS). Klebsiella pneumoniae induced higher levels of TNF-alpha than Haemophilus influenzae, Escherichia coli and Neisseria meningitidis. GGS induced higher levels of IL-6 than Staphylococcus epidermidis, Staphylococcus aureus and GAS. When the relative amounts of cytokine induced by the strains were compared to serum concentrations measured on admission in patients with bacteremia caused by the same bacterial isolates there was no significant correlation. CONCLUSION: Species- and strain-related differences in cytokine-inducing properties were found which may have significance in clinical infections.