BACKGROUND Cytokines are thought to be important endogenous mediators of the host immune response to infection. The purpose of the present study was to evaluate the utility of serum levels of interleukin (IL)-1alpha, IL-6 and tumor necrosis factor (TNF)-alpha in the prediction and differentiation of sepsis and meningitis in children. METHODS Blood was collected from 50 children admitted to hospital for suspicion of infection. On the basis of predetermined criteria and investigation, the children were classified into sepsis (n = 30) and meningitis (n = 20) groups, as well as into healthy controls (n = 24) and non-infected sick controls (n = 12). The sepsis group was subdivided according to culture results into S1 (proven sepsis, n = 11) and S2 (clinical sepsis, n = 19). Serum IL-1alpha, IL-6 and TNF-alpha were measured by enzyme-linked immunosorbent assay (ELISA) while C-reactive protein (CRP) was measured by nephelometer. RESULTS In non-infected sick controls, sepsis and meningitis groups, levels of CRP (P < 0.001, P < 0.05 and P < 0.01, respectively), IL-1alpha (P < 0.001 for all), and IL-6 (P < 0.01, P < 0.001, P < 0.001, respectively) were significantly elevated compared to healthy controls. In sepsis, levels of IL-1alpha increased in the S2 subgroup (P < 0.001) and IL-6 increased in the S1 and S2 subgroups (P < 0.05, P < 0.001, respectively) compared with healthy controls. In meningitis, IL-1alpha had the highest sensitivity and negative predictive value, while IL-6 had the highest specificity and positive predictive value in non-infected sick controls, sepsis and meningitis groups. CONCLUSIONS Interleukin-1alpha, IL-6 and CRP are increased in non-infected sick controls, sepsis and meningitis patients but it is not possible to differentiate between them. IL-1alpha had the highest sensitivity in meningitis while IL-6 had the highest specificity in prediction of sepsis and meningitis and their assessment together may improve accuracy in the diagnosis of childhood infection.