Basic fibroblast growth factor (bFGF) has been detected in body fluids of patients with various malignancies including renal cancer. Cytoplasmatic expression of bFGF in primary renal cell carcinoma cells has been reported recently to correlate with an impaired patient survival. In the present study, we analysed the statistical association of spontaneous serum bFGF levels in 23 patients with advanced renal cell carcinoma and progressive metastasis in different organ sites. Increased bFGF serum levels (>90% percentile for healthy donors i.e., > 14 pg/ml) were found in eight patients (35%) with a mean of 24.1 pg/ml. All patients in this subgroup presented with progressive pulmonary metastases at the time of sample collection (p < or = 0.007). In a total of fifteen patients exhibiting progressive pulmonary metastasis, bFGF serum levels were found to be significantly higher when compared to patients lacking progressive lung lesions (p < or = 0.0006). Of fifteen patients with bFGF levels lower than 14 pg/ml, six showed bone metastases at the time of sample collection (p < or = 0.04). Our results suggest that increased serum bFGF levels may be associated with a higher frequency of progressive pulmonary metastases. Interactions between soluble angiogenic factors and components of the extracellular matrix or basement membranes in remote sites of metastasis will be subject to further experiments.