Vascular endothelial growth factor (VEGF) is a cytokine that greatly increases vascular permeability and thereby promotes hypovolemia. The present study examines whether the plasma VEGF concentration is increased by a bolus injection of endotoxin 20 microg/kg in 30 rabbits, and whether the response is modified by vitamin A, which doubles the endotoxin clearance. The results show that endotoxin stimulates a gradual increase in the VEGF concentration to a peak 5 h later which is approximately 100 times higher than the baseline concentration. No statistically significant difference was found between the rabbits that received no further treatment (n = 10) and the ones that were given 1000 IE/kg of vitamin A intravenously 1 h before (n = 10) or after (n = 10) the endotoxin. The rise in VEGF correlated with the development of fever, and the VEGF concentrations were higher in animals with a severely affected physical status as judged by the breathing pattern and changes in posture or reactivity. In conclusion, release of VEGF is part of the cytokine response to endotoxin with a peak occurring 5 h after a bolus injection, and the rise is pronounced also in the presence of a high endotoxin clearance.