Angiogenesis is a critical step for the growth and metastasis of solid tumors, and it is a major therapeutic target for the development of anti-angiogenics for cancer treatment. Thalidomide is reported to be an anti-angiogenic agent, which is currently in phase II clinical trials for the treatment of advanced malignancies. However, the mechanism of thalidomide in angiogenesis is not completely understood. This study was undertaken to investigate the effect of thalidomide on the expression of angiogenesis growth factors in human lung cancer cells. In this report, we show that thalidomide downregulated the mRNA and protein expression of basic fibroblast growth factor (bFGF) in the human lung adenocarcinoma cell line A549, and that the effect of thalidomide was time and concentration-dependent. In contrast, the expression of vascular endothelial growth factor (VEGF) by thalidomide in these cells was in two phases. The mRNA and protein expression of VEGF was increased in the lung cancer cells treated with 0.6-6 microg/ml thalidomide, while higher concentrations of thalidomide decreased VEGF levels significantly in these cells. These data suggest that the anti-angiogenic or antitumor activity of thalidomide may be partly mediated through the regulation of the levels of angiogenesis growth factors.