Extracellular volume expansion (EVE) was performed in intact rats and 24 h after locus coeruleus (LC) lesions or sham-operation. Blood pressure was registered 5 min before and after EVE. At the end of the experiment the animals were decapitated and blood was collected from the trunk for quantification of plasma atrial natriuretic peptide (ANP). All experimental groups showed similar basal blood pressure. Volume expansion caused a slight decrease in blood pressure and an increase in ANP secretion in all groups, but these changes were significantly enhanced in animals bearing a lesion in the anterior region of the LC. There was no pronounced c-fos expression in any region of the LC 2 h after EVE in intact animals. In conclusion, the data support the idea that the LC does not participate in blood pressure control in resting conditions. However, the anterior region of the LC seems to play a role when adjustments of blood pressure and excretion of water and sodium are necessary during changes in blood volume. The results on c-fos expression are in accordance with the idea that this nucleus may be part of an inhibitory pathway which modulates the circuits of control for depressor reflex response and ANP secretion after extracellular volume expansion.