We investigated the clinical significance and regulation of serum interleukin-6 (IL-6) in patients with nasopharyngeal carcinoma (NPC). Serum IL-6 levels of 314 NPC patients and 202 healthy individuals were determined. Of the NPC patients, 69.1% (217/314) showed higher IL-6 levels than that of normal average (2.76+/-2.06 pg/ml). Elevation of IL-6 correlated with the advanced disease and the adverse prognosis of NPC patients. By employing in situ hybridization technique, IL-6 mRNA was detected in the tumor cells of NPC patients with high serum IL-6 levels. Concurrently, serum levels of butyrate were determined in 147 NPC patients and 52 healthy individuals by gas chromatography. Patients with elevated serum butyrate concentrations (4.2+/-2.2 micro M) also had significantly higher IL-6 levels (29.14+/-5.17 pg/ml). No detectable serum butyrate was measured in the healthy individuals. In order to investigate the direct relationship between butyrate and IL-6, n-sodium butyrate (n-BT) was added to the NPC cells in an in vitro study, and marked increase of IL-6 expression was detected in n-BT-treated cells. Our results suggested that tumor cells could be an important source of elevated serum IL-6 in patients with NPC and that IL-6 level in NPC patients was proportional to the serum butyrate concentration. In vitro, IL-6 expression in NPC cells could be up-regulated by butyrate.