We investigated some of the mechanisms that regulate the expression of basic fibroblast growth factor (bFGF) in human renal cell carcinoma (HRCC). HRCC SN12PM6 cells were cultured as adherent monolayers. The expression of steady-state bFGF mRNA (measured by in situ hybridization and Northern blot) and protein (measured by immunohistochemistry and ELISA) correlated inversely with the culture density. Tumor cells harvested from dense cultures (low bFGF expression) and plated under sparse conditions expressed high levels of bFGF mRNA and protein prior to cell division, suggesting that bFGF may be a competence factor. Similar data were obtained with human vascular endothelial cells. The expression of bFGF was not regulated by spent culture medium, cell cycle, or rate of cell division but was down-regulated by contract inhibition. These data show that the expression of bFGF in HRCC is cell density dependent.