Platelet endothelial cell adhesion molecule-1 (PECAM-1) is a glycoprotein that is constitutively expressed on the surface of endothelial cells, leukocytes, platelets, monocytes and neutrophils. It has been proposed that PECAM-1 plays a role in transendothelial leukocyte trafficking. In vitro studies have suggested that interferon-gamma (IFN-gamma) may regulate PECAM-1 expression on endothelial cells. We have investigated the in vivo regulatory role of mouse IFN-gamma (mIFN-gamma) on the expression of PECAM-1 on vascular endothelial cells during tumor angiogenesis. In situ retroviral gene transfer was used to deliver mIFN-gamma into established subcutaneous tumors in athymic (nu/nu) mice. The biological activity of mIFN-gamma expressed intratumorally, was verified by i) a macrophage and granulocyte (predominantly neutrophil) infiltrate observed within C6 tumors following mIFN-gamma treatment; ii) an up-regulation of major histocompatibility complex (MHC) class I and II expression on the surface of tumor cells following mIFN-gamma treatment. Indirect immunohistochemical localisation of PECAM-1 expression was performed on control and mIFN-gamma-treated C6 tumor sections. The intensity and distribution of PECAM-1 expression on vascular endothelial cells in mIFN-gamma-treated tumors was similar to control tumors. Immunohistochemical staining of PECAM-1 was compared to factor VIII-related antigen in serial tumor sections. No differences were observed between the vascular endothelial cells expressing PECAM-1 and factor VIII in serial sections of control and mIFN-gamma-treated tumors. Therefore, in this in vivo C6 tumor model, IFN-gamma does not alter PECAM-1 expression on tumor-associated vascular endothelial cells.