BACKGROUND Interleukin 6 (IL-6) is a B-cell growth and differentiation factor, which may promote the growth of B-cell neoplasms. In chronic lymphocytic leukemia (CLL) patients, IL-6 plasma levels increased in a stage-dependent manner, suggesting that IL-6 may be a useful prognostic marker. The purpose of this study is to fully assess the prognostic value of IL-6 in CLL patients. METHODS We measured the plasma levels of IL-6 in 100 CLL patients using an enzyme-linked immunoassay method. RESULTS Increasing levels of IL-6 significantly correlated with patient age, severity of anemia, Rai stage, white cell count, and beta-2-microglobulin (beta-2M). Although CLL patients did not differ significantly from the normal controls in the median IL-6 plasma level (P = 0.38), patients with advanced diseases (defined by Rai stage III/IV or beta-2M > 3.5) had a significantly higher median IL-6 plasma level than the normal controls (P < 0.05). Furthermore, in patients with advanced diseases, Cox regression hazards model showed that a higher IL-6 level correlated with shorter survival (P = 0.0001). Using IL-6 level of 3 pg/mL as a cutoff, patients with low IL-6 levels had a significantly longer overall survival than those with high IL-6 levels (log rank test, P = 0.002). In patients with CD38-positive CLL, patients with high IL-6 levels (> 3 pg/mL) had significantly shorter survival (P = 0.03). To conclude, IL-6 is a particularly useful predictor for survival in CLL patients with advanced diseases. CONCLUSIONS Our findings suggest that patients with advanced-stage CLL as well as high IL-6 plasma levels may require aggressive therapeutic approaches and special consideration for experimental therapy.