We have recently reported that an acute intragastric hypertonic saline load increases Fos immunoreactivity in several central nuclei, including the supraoptic nucleus (SON), paraventricular nucleus (PVN), nucleus of the solitary tract (NTS), area postrema (AP), and lateral parabrachial nucleus (LPBN). We have also shown that these responses are mediated by stimulation of peripheral osmoreceptors with splanchnic and vagal afferent projections. However, it is unclear whether the primary projections of peripheral osmoreceptors terminate in the NTS or the AP, both of which project to the SON and PVN. This study tested the hypothesis that efferent projections from the AP were necessary for the Fos responses in the SON, PVN, and LPBN. We examined the effect of AP lesion on the response of central Fos immunoreactivity to intragastric hypertonic saline infusion in conscious rats. Compared with sham-lesioned rats (n = 5), Fos expression in AP-lesioned rats (n = 6) was similar in the SON following the intragastric sodium load. However, in contrast to the sham group, Fos expression was significantly reduced in the PVN of AP-lesioned rats. Fos levels observed in the NTS and LPBN were similar in both groups. These results suggest that the PVN response to intragastric hypertonic saline is dependent on efferent projections from the AP. In contrast, Fos responses to this stimulus in the NTS, SON, and LPBN are independent of the activity of the AP.