In adults, marked angiogenesis takes place only during the female reproductive cycles, during wound healing, and accompanying some disease processes, such as tumor development. Vascular endothelial growth factor (VEGF) is a secreted, endothelial cell-specific growth factor, which is induced by tissue hypoxia and is angiogenic in vivo. We measured serum VEGF (S-VEGF) concentrations by ELISA in patients with a variety of types of cancer, as well as in healthy volunteers, and in patients with diabetes or rheumatoid arthritis. Elevated S-VEGF concentrations were found in patients with locoregional (n = 39; median, 158 pg/ml; range, 8-664 pg/ml) or disseminated (n = 58; median, 214 pg/ml; range, 17-1711 pg/ml) cancer in comparison to individuals without cancer (n = 113; median, 17 pg/ml; range, 1-177 pg/ml; P < 0.0001 for both comparisons). Values higher than 200 pg/ml were observed in 74% of patients with untreated metastatic cancer, and high serum levels were measured regardless of the histological type of cancer. S-VEGF levels were found to be higher in untreated patients with disseminated cancer than in those with local cancer (P = 0.006), and patients undergoing cancer therapy had lower values than those without cancer therapy (P = 0.03). The results indicate that both patients with locoregional cancer and patients with disseminated cancer may have elevated S-VEGF levels, regardless of the histological type of cancer, and that S-VEGF is often elevated in cancer with distant metastases.