Acute volume expansion is associated with a specific pattern of Fos expression and the goal of the present study was to evaluate the contribution of cardiac receptors to this response. Adult male rats were instrumented with pericardial catheters introduced at the level of the thymus. Rats were also catheterized for measuring blood pressure, heart rate, central venous pressure, and intravenous infusion. Each rat received a 200-μl intrapericardial (i.p.c) injection of 2% procaine or 0.9% NaCl. Rats were then volume expanded with isotonic saline (10% body weight in 10 min) or given a control infusion (0.01 ml/min for 10 min). Ninety minutes after the start of the infusion, the rats were anesthetized and perfused transcardially. Their brains were sectioned and processed for Fos, dopamine-β-hydroxylase, and oxytocin immunocytochemistry. Volume expansion plus i.p.c. saline produced a significant increase in Fos expression in the nucleus of the solitary tract, the ventrolateral medulla, the area postrema, the locus coeruleus, the paraventricular nucleus of the hypothalamus, the perinuclear zone of the supraoptic nucleus, and oxytocin neurons in the supraoptic nucleus. The i.p.c. procaine significantly blocked Fos expression produced by the volume expansion in the all of the regions examined except for the area postrema and the SON oxytocin neurons.