Pro-inflammatory cytokines are dysregulated in schizophrenia. To determine the nature of the so-called inflammatory syndrome in schizophrenia, we investigated the circulating levels of various cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)α), their natural antagonists (IL1-ra, TNF-RI, TNF-RII) and leukocyte activation markers (the soluble receptor of interleukin-2, soluble CD14 and soluble CD23) in subjects with chronic schizophrenia (n=18) and in normal controls (n=21). The levels of IL-1β and its antagonist and the levels of leukocyte activation markers were not significantly differents between patients and controls. Circulating levels of TNFα were significantly (p<0.05) higher in patients than in controls and did not result from variations of its antagonist levels. The significant (p<0.05) increase in patient IL-6 was related specifically to clinical status, i.e. illness duration. These data suggest a specific cytokine-mediated syndrome in schizophrenia. We hypothesize that TNFα and IL-6 reflect the genetic background of disease suceptibility.