Surgical biopsies from ten head and neck squamous cell carcinomas were labeled in vitro with bromodeoxyuridine. In histological sections, bromodeoxyuridine-positive nuclei and β-fibroblast growth factor (β-FGF) were stained using immunohistochemistry. In clearly discernible clusters of tumor cells, the cytoplasm shows strong positive β-FGF staining, whereas other tumor regions are completely β-FGF negative. Within positively stained areas, the tumor cell bromodeoxyuridine labeling index is higher in comparison to β-FGF-negative areas by a factor of 5 ± 0.8. This is reflected in a positive correlation of the tumor cell labeling index and the relative extent of β-FGF-positive tumor areas. Viable tumor areas bordering on necrosis, which are known to be hypoxic, are β-FGF negative. The average tumor endothelial cell labeling index was 1.8 ± 0.6%, as compared to 0.16% in adjacent normal mucosa. Since endothelial cell pulse labeling indices are too low for a further quantitative analysis, the relationship of β-FGF expression and endothelial cell turnover was studied in more detail in two fairly well-differentiated murine squamous cell carcinoma lines (AT 84 and AT 478). Labeling indices were higher and endothelial cell doubling times were significantly shorter in β-FGF-positive as compared to β-FGF-negative tumor areas (AT 84, 9.3 h versus 25.4 h; AT 478/25, 6.8 h versus 16 h). Thus, the discrete expression of β-FGF is associated with regional differences in endothelial cell kinetics. In two generations of the tumor line AT 478, characterized by different volume doubling times of 18 days (AT 478/25) and 36 days (AT 478/4), β-FGF-positive areas represent 75.5 ± 6% and 19.7 ± 7% of the viable tumor tissue, respectively. This indicates a correlation between β-FGF production of tumor cells and growth rate.