Inhibition of angiogenesis provides a potential anti-cancer therapy. Here we describe a novel recombinant peptide composed of active fragments of two distinct angiogenesis inhibitors, platelet factor-4 (C-13 fragment) and vasostatin (N-terminal amino acids 135-164) with a nonpolar peptide bridge of Gly-Pro-Gly. This fusion peptide showed significantly enhanced efficacy compared with its parent peptides in inhibiting human endothelial cell proliferation and neovasculerization in chick embryo chorioallantoic membrane. The data suggest that making a single recombinant peptide containing the active fragments of multiple angiogenesis inhibitors is a promising approach to developing a better anti-angiogenetic therapy.