The physiological actions of the natriuretic peptides are first modulated by interactions with their receptors. The NPR-A receptor recognizes the atrial natriuretic peptide (ANP) and the NPR-B receptor shows specificity for the natriuretic peptide type-C (CNP). In this study we investigated the effects of combined injections of ANP or CNP in the lateral ventricle (LV) on water and 0.3M NaCl intake in rats submitted to 24 h of sodium depletion or water deprivation. Methods and Results: Male Wistar rats (250-300 g, n = 5-8) with sham or stainless steel cannulas implanted into the lateral ventricle (AP= 0.8 mm caudal to bregma; L=1.2 mm lateral to midline and V=4 mm bellow dura mater) were used. All surgical procedures were performed under ketamine (80 mg/kg of body weight) combined with xylazine (7 mg/kg of body weight) anesthesia. Water and 0.3 M NaCl intake was induced by water deprivation (the rats had water bottles removed from the cages with free access to food for 24 h) or sodium depletion [the rats received a subcutaneous injection of the diuretic Furosemide (20 mg/kg,0.2 ml/kg) followed by access to sodium deficient diet and water for 24 h]. ANP (1 µg/5 µl) or CNP (1 µg/5 µl) were injected consecutively in the LV with a range interval of 10 min. Sham rats received only vehicle in the LV. At the end of the injections, two glass burettes with 0.1 ml divisions containing 0.3 M NaCl or water were offered to rats and the intake was measured every 15 min for 1h. Values are means ± S.E.M., compared by ANOVA. Results: Lateral ventricle injection of ANP plus CNP reduced 0.3 M NaCl intake in response to water deprivation (1.4 ± 0.4 ml vs. sham: 5.3 ± 1.5 ml, p = 0,01) and sodium depletion (3.2 ± 1.2 ml vs. sham: 8.0 ± 2.5 ml, p < 0,05) without changes on water intake. Also, CNP plus ANP reduced 0.3 M NaCl intake (1.8 ± 0.5 ml) only in response to water deprivation. There were no changes on sodium intake in rats previously treated with CNP plus ANP in the LV and subjected to sodium depletion. This last result shows that the previous injection of CNP was able to inhibit the inhibitory effect of ANP on sodium intake. A decrease in water intake was observed when CNP plus ANP were administered into the LV in response to water deprivation (3.7 ± 1.4 ml vs. sham: 16.8 ± 4.5 ml, p < 0,05) and sodium depletion (0.5 ± 0.2 ml vs. sham: 1.6 ± 0.5 ml, p < 0,05). Conclusion: In rats subjected to intra- or extracellular thirst, the results are pioneers in demonstrating an inhibitory modulation of the ANPergic pathway on the CNPergic path in rats previously treated with ANP plus CNP in the LV reducing sodium appetite; as well as the previous injection of CNP plus ANP reducing water intake.