Inflammatory cytokines play important roles in the pathogenesis of lymphomas and may reflect underlying biological processes including tumour-host interactions with prognostic information that is not afforded by conventional clinical parameters. Several lines of evidence suggest that serum levels of interleukin (IL)-6 and vascular endothelial growth factor (VEGF) are independent indicators of long-term outcome in non-Hodgkin's lymphoma (NHL), but the clinical impact of early serial monitoring of these cytokines has not been reported. Serum samples from 64 newly diagnosed patients with aggressive NHL were obtained before the first cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and then weekly until the second cycle was given. Serum IL-6 and VEGF were measured by commercial enzyme-linked immunosorbent assays (ELISA). Pre-treatment serum IL-6 and VEGF levels were significantly correlated to response rate and overall survival. A significant decrease of IL-6 and VEGF levels was observed in the first weeks after CHOP therapy in patients achieving a complete remission after treatment. Multivariate analysis indicated that early changes of IL-6 and VEGF serum levels within the first 3 weeks after initiation of chemotherapy were independent predictors of clinical response even when corrected for the influence of clinical prognostic factors. Only changes in serum IL-6 level had borderline significance for the prediction of overall survival. The data indicate that serial measurements of serum IL-6 and VEGF may be early prognostic indicators and support the hypothesis of a clinical impact by early recognition of poor-risk patients and candidates for new treatment options.