Vascular targeting is currently being explored as a new therapy for pancreatic cancer, and a promising new target is phosphatidylserine (PS). PS is an anionic phospholipid normally located on the inner leaflet of the plasma membrane. Oxidative stress in the microenvironment of tumors causes PS exposure on the surface of endothelial cells. PS-positive endothelial cells are functional and not apoptotic. PS is absent from the endothelium of normal tissues, and is therefore a highly specific marker of tumor vessels. The antibody 3G4 binds PS and inhibits growth of a variety of tumors in mice. Here we highlight 3G4 as a treatment of pancreatic cancer in a mouse model. Inhibition of primary tumor growth and metastases at all sites was significant with 3G4 alone, and significantly enhanced by combination with gemcitabine. Thus, the combination of PS-targeting and gemcitabine might be an effective new drug combination for treatment of pancreatic cancer.© 2006 John Wiley & Sons, Ltd.