Several lines of evidence suggest that peripheral osmoreceptors respond to alterations in dietary NaCl by adjusting renal sympathetic nerve activity, but the impact of this reflex on the long-term regulation of mean arterial pressure (MAP) remains unclear. The present study tested the hypothesis that denervation of peripheral osmoreceptors elevates arterial pressure and induces NaCl-sensitive hypertension in normotensive rats. Hepatic denervated and sham-operated Wistar-Kyoto rats were instrumented with telemetry probes for continuous monitoring of MAP and heart rate. After 1 week on a basal (0.6%) NaCl diet, the rats were fed a high (8%) NaCl diet for 2 weeks. On the basal NaCl diet, MAP in hepatic denervated rats was 15±1 mm Hg higher than in sham-operated rats. The high NaCl diet did not significantly increase MAP above baseline levels in either denervated or sham-operated rats, but the amplitude of the 24-hour rhythm of arterial pressure increased significantly more in the denervated than in the sham-operated rats. In a second experiment, two similar groups of rats were fed a very low (0.05%) NaCl diet. Mean arterial pressure of the denervated group was significantly higher than that of the sham-operated rats on either the basal or the very low NaC1 diet, but the very low NaC1 diet did not affect arterial pressure in either group. These results suggest that in the rat, although hepatic osmoreceptors contribute to long-term arterial pressure regulation, they contribute much less to dietary NaCl-induced changes in arterial pressure.