Angiopoietin (Ang) 1 and Ang-2 are important regulators of endothelial cell survival. Current models suggest that an increase in Ang-2 expression in endothelial cells leads to initiation of angiogenesis. We stably transfected HT29 colon cancer cells with cDNA constructs for Ang-1 or -2 or with vector alone, injected the cells s.c. into nude mice, and assessed tumor growth. Immunohistochemical analyses confirmed sustained increases of Ang-1 and -2 in the tumors. The tumors produced by the Ang-2-transfected cells were larger than the tumors produced in the other groups; those tumors also had higher vessel counts and proliferative indices than tumors in the other groups. Tumors produced by the Ang-1 transfectants had fewer vessels and lower tumor cell proliferative indices than tumors in the other groups. These data suggest that imbalances between Ang-1 and -2 that result in a net gain of Ang-2 activity lead to enhanced tumor angiogenesis and growth.