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We have designed short peptides composed of two functional domains, one a tumor blood vessel'homing'motif and the other a programmed cell death-inducing sequence, and synthesized them by simple peptide chemistry. The'homing'domain was designed to guide the peptide to targeted cells and allow its internalization. The pro-apoptotic domain was designed to be nontoxic outside cells, but toxic when internalized into targeted cells by the disruption of mitochondrial membranes. Although our prototypes contain only 21 and 26 residues, they were selectively toxic to angiogenic endothelial cells and showed anti-cancer activity in mice. This approach may yield new therapeutic agents.