Angiogenesis, the growth of new capillaries from preexisting blood vessels, is essential for tumour growth and the development of metastases. Vascular endothelial growth factor is the most potent angiogenic factor identified to date Tamoxifen has been shown to inhibit angiogenesis m a manner independent of the oestrogen receptor. The expression of VEGF in breast cancer, possible regulators, and evidence for a VEGF related inhibition of angiogenesis by tamoxifen was examined. BT474 and MDA-MB-231 cells are breast cancer cell lines of primary and metastatic origin, respectively. Both cell lines expressed VEGF protein and mRNA with the MDA-MB-231 cell line producing 5 fold more VEGF than the BT474 cell line VEGF protein was elevated in breast tumour tissue as compared to matched normal tissue. Serum VEGF levels were significantly elevated in patients with breast cancer compared to patients with benign fibroadenomas and age-matched healthy controls. The expression of TGF(3-1 was found to be associated with the expression of VEGF in the serum and tumour tissue of breast cancer patients. TGFp-1 increased expression of VEGF by both breast cancer cell lines. Tamoxifen significantly decreased serum levels of VEGF m breast cancer patients independently of oestrogen receptor status. Tamoxifen did not reduce VEGF production by either breast cancer cell lines or by macrophages, important contributors of breast tumour VEGF. Tamoxifen decreased monocyte transendothelial migration in vitro From these results we conclude that the expression pattern of VEGF suggest a role for this factor in breast cancer. TGFp-1 is a regulator of VEGF expression m breast cancer. Tamoxifen reduces serum VEGF levels and in an in vivo situation this may be achieved by reducing endothelial migration and tumour recruitment of macrophages and, thereby reducing overall tumour production of VEGF.