Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality; however, some patients with OSA do not develop cardiovascular disease even in the presence of severe nocturnal oxygen desaturations. Vascular endothelial growth factor (VEGF) is a hypoxia-sensitive glycoprotein stimulating neoangiogenesis. We hypothesized that VEGF production is increased in OSA because of repetitive nocturnal hypoxia. Three different groups were investigated: 10 OSA patients with severe nighttime hypoxia (Group A), 10 OSA patients with moderate hypoxia (Group B), and 10 healthy volunteers (Group C). Serum levels of VEGF were measured by ELISA from peripheral venous blood samples obtained at 7 AM. Group A had significantly (p < 0.01) increased VEGF serum levels when compared with Group B and Group C (mean +/- SEM: 410 +/- 77 pg/ml versus 224 +/- 38 pg/ml and 245 +/- 61 pg/ml). The degree of nocturnal oxygen desaturation in OSA significantly correlated with the VEGF concentrations (r = 0.67, p < 0.01). In conclusion, serum levels of VEGF are elevated in severely hypoxic patients with OSA and are related to the degree of nocturnal oxygen desaturation. This might constitute an adaptive mechanism to counterbalance the emergence of OSA-related cardiovascular disease.