Metastatic brain tumors are almost always associated with vasogenic brain edema, which in turn plays a pivotal role in the evolution of neurological morbidity associated with these lesions. Attention has recently focused on a group of proteinaceous vascular permeability factors (VPF's) that are capable of inducing angiogenesis and promoting increased capillary permeability. To test the hypothesis that metastatic brain tumors expressing VPF's are associated with peritumoral cerebral edema, a rabbit polyclonal immunoglobulin (Ig) G anti-VPF was used to immunostain pathological specimens of metastatic cerebral tumors obtained from 22 patients who underwent surgery at Yale-New Haven Hospital. Magnetic resonance (MR) imaging was used to correlate VPF staining in tumor tissue with the occurrence of peritumoral brain edema. A histological study of the microvasculature was then conducted by immunostaining the specimens for endothelial cell factor VIII surface antigen, using two gliosis specimens as controls. Results revealed 21 of 22 tumors stained positively for VPF's; the negative-VPF tumor was a melanoma that exhibited no peritumoral edema. Twenty of 22 tumors had MR imaging-evident vasogenic edema. The presence and intensity of VPF immunostaining of microvascular features were noted and compared. Factor VIII staining demonstrated tumor vascularity to be most abundant in VPF-rich regions of tumor. The authors therefore report a high correlation between the presence of VPF's and the occurrence of peritumoral brain edema associated with cerebral metastases.