DBA/2 mice were injected sc with cells from the highly malignant Friend erythroleukemia cell (FLC) 3C18 subline, which is resistant to mouse interferon α/β, or with the ESb lymphoma. When interferon alp was injected intratu-morally or peritumorally, tumor growth was markedly sup-pressed, and established vascularized tumor nodules became progressively necrotic. Tumor necrosis was of the coagu-lation type that usually results from deprivation of bloodflow. Morphologic examination of ∼1,000 blood vessel pro-files and ∼2,000 endothelial cells in 1-υm Epon sectionsof sc 3CI8 FLC tumors showed that interferon treatment resulted in rapid and pronounced vascular end othelial celldamage that preceded tumor necrosis. No inflammatory cellinfiltrate was observed. Our results suggest that interferon α/β exerted an antitumor effect in these tumor models bydamaging tumor blood vessels, causing disruption of tumorblood flow, which led to ischemic tumor necrosis. [J NatlCancer Inst 81:497-502, 1989]