Secretion of FGF-1 has been demonstrated to occur in association with biological stress. During inflammation, endothelial cells may be subjected to oxidant stress and locally generated cytokines/growth factors associated witli induction of adhesion molecules. Consequently, effects of FGF-1 in the presence and absence of IL-l and TNFa on expression of ICAM-1 were determined in vitro using primary HUVEC cultures. Basal expression of ICAM-1 (by ELISA) in HUVEC engineered (retrovirallymediated) to secrete FGF-1 was 164% of levels determined in controltransduced cells. Induction of ICAM-1 expression in response to IL-1β (100 U/ml) exposure (16 hr) was significantly (p<.01) greater for FGF-1 secreting HUVEC (255 ±17 % of basal levels) than for controltransduced cells (195 ± 27 % of basal levels). IL-1β induced expression ot ICAM-1 in non-transduced HUVEC (156 ±18%) was enhanced by exogenous recombinant FGF-1 224 ±50), an observation restricted to growth factor exposure 1 -8 hours before or one hour after treatment with ihe cytokine. Extracellular FGF-1 had no significant effect on ICAM-1 expression induced by TNFa. Collectively these observations suggest that extracellular FGF-1 enhances endothelial cell expression of ICAM-1, including that induced by IL-1β, by a mechanism involving early signal Iransduction processes rather than cellular proliferation.