Stimulation of the atrial volume receptors increases neural traffic to the ventrolateral medulla, which in turn sends output to, and receives input from, the lateral hypothalamic area. An integrated reflex and hormonal response is thus initiated. We wished to investigate first whether atrial distension results in activation of selected nuclei in the forebrain and, second, whether pregnancy modifies this response. Rats were implanted with indwelling intracardiac balloons positioned at the superior vena caval/right atrial junction. One week later, the balloons were inflated. The animals were then anesthetized, their brains fixed by perfusion, and the tissue prepared for visualization of c-fos activity. Atrial distension caused a significant increase in c-fos expression in the paraventricular nucleus, the medial preoptic area, and the lateral septum. This response was markedly attenuated in the pregnant animals. In conclusion, during pregnancy central pathways that are normally activated in responses to volume expansion, fail to respond to atrial distension. We propose that this allows blood volume to increase in the pregnant animal, without triggering homeostatic mechanisms.