OBJECTIVE: To evaluate the sensitivity of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) plasma measurement to detect bacteremia in patients presenting sepsis signs, and to evaluate the potential benefit of such measurement in terms of early antimicrobial therapy initiation. METHODS: Plasma was obtained from 166 hospitalized patients for whom blood cultures were drawn for sepsis. Clinical data and antimicrobial therapies were noted. IL-6, TNF and C-reactive protein (CRP) were measured. The sensitivities of these markers were retrospectively compared with the accuracy of the attending physician in initiating empirical antimicrobial therapy. The setting was an 850-bed university hospital. RESULTS: Thirty-four bacteremias and 69 non-bacteremic infections were noted. In 63 others, no infection was documented. Median (range) IL-6 plasma levels in the three groups of patients were 462 (15--50 850), 189 (<15--38 300) and 91 (<10--13 750) pg/mL, respectively (p<0.01). The corresponding TNF-alpha plasma levels were 37.5 (<15--2400), 15 (<15--240) and 15 (<15--200) pg/mL, respectively (p<0.01). CRP plasma levels were 10.7 (<0.6--30.2), 10.3 (<0.6--34.4) and 7.3 (<0.6--20.9) mg/dL, respectively (p=0.12). With respect to these three parameters, IL-6 and TNF-alpha appear better than CRP for predicting bacteremia. Clinical features resulted in starting empirical antimicrobial therapy in only 62% of the bacteremic patients. On the other hand, 68% of these bacteremic patients had high IL-6 plasma levels (>200 pg/mL). A combination of clinical features and high IL-6 levels would have permitted early treatment for 82% of the bacteremic patients. CONCLUSIONS: IL-6 and TNF-alpha thus appear to be useful and earlier markers of bacteremia in septic patients. By contrast, CRP is neither sensitive nor specific in this setting.