The roles of basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) in vein disease and aging were investigated. Smooth muscle cells from human saphenous veins were cultured. The age dependence of bFGF and PDGF activation of the smooth muscle cell proliferation was determined, and the bFGF and PDGF contents in vein wall homogenates were measured by an enzyme-linked sorbent assay. There were morphological alterations in the cells with more polygonal and polynucleated cells in cultures from aged donors, similar to those observed in vitro in aged cell cultures. Some cultures did not reach confluency after the tenth passage, suggesting early decay of the cultures from diseased veins. bFGF and PDGF stimulated the proliferation of the vein smooth muscle cells, but only in cultures treated with hyaluronidase. This stimulation decreased with the age of the donor. The amount of the two growth factors in human vein walls decreased with donor age. The amount of bFGF decreased faster (slope: 3.3138 ng/mg DNA/year) than that of PDGF (slope: 1.021 ng/mg DNA/year). This results in an age-dependent change in the bFGF/PDGF ratio from 4 mol/mol at the age of 20 years to 1 mol/mol at the age of 80. These growth factors also modulate the synthesis of extracellular matrix components. The continuous change in the bFGF/PDGF ratio may alter the composition of the extracellular matrix of the vein wall during aging and thus its susceptibility to varicose disease.