Basic fibroblast growth factor (bFGF) is a potent nitogen and angiogenic protein that may function as an autocrine growth regulator in a variety of malignancies. Expression of bFGF in squamous cell carcinoma of the head and neck (SCCHN) was characterized by Western blot and immunohistochemical analyses. We found that the levels of bFGF in tumors were the same or reduced relative to non-malignant adjacent mucosa. Reverse transcription-polymerase chain reaction and Southern blot transfer of mRNA derived from 7 SCCHN cell lines showed that the IIIb isoform of FGF-receptor 2 (FGFR2) was expressed at high levels, whereas the IIIc isoform and FGFRI were weakly expressed or not detected. No correlation was observed between levels of bFGF revealed by immunohistochemical staining and vascular counts in frozen sections derived from 11 different SCCHN tumors. Immunohistochemical analysis demonstrated that all differentiated tumors exhibited high levels of bFGF immunoreactivity, while all poorly differentiated tumors exhibited low to nondetectable levels. This expression pattern is consistent with that observed in non-tumoral mucosa and suggests that other angiogenic factors must play a predominant role in the development of poorly differentiated SCCHN.