Uremia, when treated with chronic dialysis, accelerates atherogenesis and its attendant complications. Using a chronic exposure modelin vitro, it has previously been shown that uremic concentrations of oxalic acid inhibit endothelial cell (EC) proliferation and migration. In this paper the permeability of ECs to oxalate and the effect of oxalate on the proliferation of ECs stimulated by heparin-binding growth factors are studied. ECs were permeable to [14C]oxalate with uptake dependent on external oxalate concentration and efflux dependent on temperature, time, and external oxalate concentration (allP<0.0001). The proliferation of unstimulated cultures and cultures stimulated with basic fibroblast growth factor (bFGF), endothelial cell growth supplement,αendothelial cell growth factor andβendothelial cell growth factor was inhibited by exposure to oxalate in all experiments from 14 to 100% in 14 to 60 d (N=19, allP<0.001). Furthermore, surviving cultures were converted from the proliferative to the quiescent state. The proliferation of neither fibroblasts nor BALB/c 3T3 cells was altered by oxalate. Oxalate modified neither the binding of [125I]bFGF to specific EC membrane receptors nor receptor density. Furthermore, oxalate did not interfere with the interaction of bFGF and its cofactor heparin. We conclude that uremic concentrations of oxalate inhibit the proliferation of ECs stimulated with heparin-binding growth factors.