The in vivo model of the chick embryo chorioallantoic membrane (CAM) was used to study the involvement of nitric oxide (NO) in angiogenesis. The nitrovasodilator sodium nitroprusside (NaNP) and the amino acid, L-arginine, inhibited angiogenesis, assessed as both collagenous protein biosynthesis and vascular density. NG-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, increased both collagenous protein biosynthesis and vascular density, indicating that this agent promotes angiogenesis. These results suggest that NO may participate in the regulation of angiogenesis. Manipulation of NO synthesis therefore, may prove to be another approach for controlling angioproliferative diseases.