Basic fibroblast growth factor (bFGF) is closely involved in angiogenesis and tumor growth of various cancers, but its role in proliferation and differentiation of non-small cell lung cancer (NSCLC) remains to be defined. The majority of NSCLC cell lines produce elevated protein levels of bFGF but do not secrete comparable amounts. We therefore investigated the influence of bFGF on the proliferation of three human NSCLC cell lines. Our experiments demonstrate that intracellular bFGF level and bFGF mRNA expression correlated with the proliferation rate in all three cell lines. Delivery of a bFGF neutralizing monoclonal antibody, anti-sense oligonucleotides or a vector expressing bFGF antisense cDNA into the cells inhibited tumor cell growth. Delivery of recombinant bFGF into a bFGF-negative cell line led to increased proliferation. These findings suggest that bFGF stimulates the growth of tumor cells by intracrine mechanisms. Strategies to inhibit bFGF in NSCLC may therefore be a promising approach in NSCLC therapy.