We examined c-Fos and FosB staining in the central nervous system 8 and 24 h following acute volume expansion in unanesthetized rats. Male rats were instrumented with a femoral artery catheter for measurement of blood pressure and heart rate (HR), a jugular venous catheter for measurement of central venous pressure (CVP), and a femoral vein catheter for i.v. infusion. After 48 h, rats were volume expanded with isotonic saline (10% of body weight for 10 min i.v.) or given a control infusion (0.01 ml/min for 10 min i.v.). After a period of 8 or 24 h, the rats were deeply anesthetized and perfused transcardially with 4% paraformaldehyde. Separate sets of serial sections of the hypothalamus were processed for either FosB (Santa Cruz) or c-Fos (Oncogene AB-5) immunocytochemistry. The volume expansion protocol significantly increased central venous pressure but did not affect blood pressure or heart rate. Volume expansion produced a significant increase in FosB-positive cells in the paraventricular nucleus (PVN) of the hypothalamus, the supraoptic nucleus (SON), the perinuclear zone (PNZ) of the supraoptic nucleus, the nucleus of the solitary tract (NST), and the caudal ventrolateral medulla (CVL) in both the 8- and 24-h groups. In the area postrema (AP), the number of FosB-positive cells was significantly increased only at 8 h post-infusion. However, c-Fos was not significantly increased above control levels at either time point. The results demonstrate that FosB activation is maintained for at least 24 h following an acute increase in central venous pressure.