Prediction of survival for patients with metastatic breast cancer is often inaccurate and may be helped by new biological parameters. Tumour growth being angiogenesis-dependent, it has been hypothesised that the assessment of angiogenic factor production might reflect the clinical behaviour of cancer progression. This study was designed to investigate the clinical significance of vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) in hormone-refractory metastatic breast cancer. Serum and plasma concentrations of VEGF and serum concentration of IL-6 were measured in 87 patients with a fully documented history of metastatic breast cancer using an enzyme-linked immunoassay. All patients had detectable levels of VEGF, whereas 39% patients had detectable serum levels of IL-6. There was a positive correlation between IL-6 levels and the theoretical VEGF load of platelets (P<0.001). The presence of high levels of serum IL-6, but not VEGF, was significantly correlated to a shorter survival. In a multivariate analysis along with clinical prognostic parameters, serum IL-6 was identified as an independent adverse prognostic variable for overall survival (P&<0.001). These results indicate that serum IL-6 levels correlate to poor survival in patients with hormone-refractory metastatic breast cancer. Vascular endothelial growth factor serum and plasma levels are not useful indicators of prognosis for these patients.