IL-1β and IL-1α are essential for tumor invasiveness and angiogenesis. In IL-1β knockout (KO) mice, B16 melanoma cells failed to form local tumors or metastases, while angiogenesis in Matrigel plugs was absent. Exogenous IL-1 restored angiogenesis, and IL-1 receptor antagonist (IL-1Ra) inhibited it. IL-1α KO mice showed reduced tumor growth and angiogenesis compared to WT, but higher than IL-1β KO. These effects were observed in other tumor models, including DA/3 mammary and prostate cancer. IL-1 also promotes vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNFα) production in macrophage-tumor cocultures. Host-derived IL-1 controls tumor angiogenesis and invasiveness. IL-1Ra, which inhibits IL-1 activity, may have therapeutic potential in cancer, in addition to its use in rheumatoid arthritis. IL-1β is secreted into the tumor microenvironment, activating stromal cells and malignant cells, while IL-1α is cell-associated. IL-1β is more critical for tumor progression, while IL-1α plays a greater role in DA/3 mammary cancer. IL-1Ra inhibits angiogenesis and tumor growth, suggesting its potential as an anti-angiogenic therapy.IL-1β and IL-1α are essential for tumor invasiveness and angiogenesis. In IL-1β knockout (KO) mice, B16 melanoma cells failed to form local tumors or metastases, while angiogenesis in Matrigel plugs was absent. Exogenous IL-1 restored angiogenesis, and IL-1 receptor antagonist (IL-1Ra) inhibited it. IL-1α KO mice showed reduced tumor growth and angiogenesis compared to WT, but higher than IL-1β KO. These effects were observed in other tumor models, including DA/3 mammary and prostate cancer. IL-1 also promotes vascular endothelial growth factor (VEGF) and tumor necrosis factor α (TNFα) production in macrophage-tumor cocultures. Host-derived IL-1 controls tumor angiogenesis and invasiveness. IL-1Ra, which inhibits IL-1 activity, may have therapeutic potential in cancer, in addition to its use in rheumatoid arthritis. IL-1β is secreted into the tumor microenvironment, activating stromal cells and malignant cells, while IL-1α is cell-associated. IL-1β is more critical for tumor progression, while IL-1α plays a greater role in DA/3 mammary cancer. IL-1Ra inhibits angiogenesis and tumor growth, suggesting its potential as an anti-angiogenic therapy.