Sleep apnea syndrome is associated with recurrent episodic hypoxia during sleep, which has been implicated in the development of cardiovascular morbidity. Hypoxia is the major stimulus of vascular endothelial growth factor (VEGF), which is a potent angiogenic cytokine. In the present article we describe the results of three experiments in which plasma concentrations of VEGF were measured in patients with sleep apnea. In Experiment 1, apnea-hypopnea index was found to be a significant independent predictor of morning VEGF concentrations in 85 male subjects investigated in the sleep laboratory, of whom 47 had an apnea-hypopnea index greater than 20. In Experiment 2, VEGF concentrations measured hourly during the sleep period were found to be significantly higher in a group of five sleep apnea patients compared with six age-similar snorers and six normal young adults (129.1 +/- 43.4 versus 74.6 +/- 11.5 and 32.5 +/- 12.8 pg/ml, respectively [p < 0.007]). In Experiment 3, VEGF concentrations were compared in patients with sleep apnea before and 1 year after nasal continuous positive airway pressure treatment. A significant decrease in VEGF concentrations was found only in patients in whom nocturnal hypoxia improved after treatment (57.1 +/- 62.5 versus 39.6 +/- 46.9 pg/ml, p < 0.01). There was no comparable improvement in patients who did not accept treatment (53.9 +/- 23.6 versus 54.0 +/- 21.5 pg/ml, ns). These results raise the possibility that VEGF may contribute to the long-term adaptation of sleep apnea syndrome to recurrent nocturnal hypoxia.