We have previously demonstrated that somatostatin analogues SMS 201-995 and RC-160 inhibit angiogenesis using the chorioallantoic membrane (CAM) of the developing chicken embryo. In this study, we evaluated the ability of native somatostatin 14 and nine somatostatin analogues to inhibit angiogenesis. Two-millimeter methylcellulose disks containing 50 micrograms of somatostatin or somatostatin analogue were implanted on the CAM of 6- to 7-day-old shell-less chick embryos. Inhibition of blood vessel growth was visually assessed and graded in the region of the disk 24-36 hr following implementation. The analogues SMS 201-995 and RC-160 showed statistically significant inhibition of neovascularization when compared to native somatostatin 14. The amino acid homology comparison of the nine analogues revealed that individual differences in their abilities to inhibit angiogenesis may be structurally dependent.