The binding characteristics of basic fibroblast growth factor (bFGF) to membranes prepared from four human breast cancer cell lines (BT-20; MCF-7; MDA-MB-231; T-47D) have been investigated. Scatchard analyses of competition experiments indicate one class of specific binding sites in MCF-7 and T-47D cells, and two classes of specific binding sites in BT-20 and MDA-MB-231 cells. The presence of high affinity sites was demonstrated in each cell type. These results have been confirmed using saturation experiments. Chemical crosslinking of labeled bFGF in breast cancer cell lines followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed one specific complex with a relative molecular mass of about 85,000. A second class of lower affinity binding sites was detected only in the two hormone-independent cell lines. bFGF stimulation of proliferation has also been demonstrated in MCF-7, T-47D, and BT-20, but not in MDA-MB-231, which has a high proliferation activity without the addition of growth factors. These suggest that the presence of bFGF specific binding sites in human breast cancer cell membranes is a necessary but not sufficient condition for exogenous bFGF growth stimulation of these cells; they also suggest that FGF plays a role in breast cancer.