Vascular endothelial growth factor (VEGF) is used to evaluate the angiogenic activity in breast carcinoma. Nitric oxide (NO) and insulin-like growth factor-I (IGF-I) are also implicated in breast tumorigenesis, including angiogenesis. We measured serum VEGF, IGF-I and nitrate+nitrite levels in 38 patients with metastatic and 23 with nonmetastatic breast cancer and in 16 controls. Serum VEGF and IGF-I levels were higher in patients with metastatic disease than in those with nonmetastatic disease or in controls (P<0.001). Serum nitrate+nitrite levels were higher in patients with metastatic and nonmetastatic disease than in controls (P<0.001). Patients with visceral metastasis and local metastasis had higher serum VEGF and nitrate+nitrite levels than patients with bone metastasis (P<0.05). In the metastatic disease group, there was a positive correlation between serum VEGF levels and nitrate+nitrite levels (r=0.436, P<0.05). Within the group with nonmetastatic disease, premenopausal patients had higher serum IGF-I levels than did postmenopausal patients (P<0.001). NO may involve an angiogenic process that is stimulated by VEGF in breast carcinoma. Larger studies are required to clarify these suggestions.