Endocrine disrupting chemicals (EDCs) can behave as agonists or antagonists of several hormone receptors, thus mimicking or antagonizing the physiological activity of endogenous ligands. The involvement of estrogens in the regulation of angiogenesis has convincingly been demonstrated by a large body of experimental studies. Some polychlorobiphenyls (PCBs), considered EDCs, interact with estrogen receptors (ERs), so it is possible that these exogenous compounds affect the angiogenic process. Using fluorescence polarization, we firstly assayed whether PCB 77 (3,3',4,4'-tetrachlorobiphenyl), PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl) and PCB 156 (2,3,3',4,4',5-hexachlorobiphenyl) were able to bind to the alpha isoform of ER, recently found to be involved in angiogenesis. To discriminate the putative agonist or antagonist binding behaviour of these compounds, we tested their ability to activate, similarly to the natural ligand 17-beta-estradiol (17betaE(2)), the extracellular-signal-regulated kinase (Erk) 1/2 in human umbilical vascular endothelial (HUVE) cells. Finally, by using a new angiogenic assay, we evaluated the effect of PCBs treatment on microvessels neoformation. The data obtained in the present study showed that all the PCBs tested were able to bind to ERalpha and to elicit a response which can be agonistic or antagonistic; moreover, PCB 153 and PCB 77 can either positively or negatively modulate the angiogenic process, thus behaving as EDCs in endothelial cells.