Vascular endothelial cells sense and respond to pressure by molecular mechanism(s) which, to date, remain poorly understood. The present study investigated basic fibroblast growth factor (bFGF) signaling as a putative mechanotransduction pathway involved in the proliferative responses of human umbilical vein endothelia cells (HUVECs) to 60/20 mm Hg cyclic pressure at 1 Hz for 24 h. Under these conditions, the enhanced proliferative response of these HUVECs was not associated with an increased synthesis/release of bFGF, but involved rapid (within 30 min from the onset of exposure to pressure) tyrosine phosphorylation of the bFGF receptor, FGFR-2. Furthermore, monoclonal antibodies to either bFGF or FGFR-2 attenuated the increased proliferation of HUVECs exposed to 60/20 mm Hg cyclic pressure. HUVECs proliferation under 60/20 mm Hg at 1 Hz cyclic pressure is, therefore, dependent upon bFGF and involves FGFR-2 activation.