An anteroventral third ventricle (AV3V) lesion in the brain prevents several forms of experimental hypertension. The present experiment was designed to determine whether the AV3V lesion prevents NaCl-induced hypertension in Dahl salt-sensitive (S) rats and whether attenuation of vasopressin release reported in lesioned rats contributes to the protective effect of the AV3V lesion against hypertension. After the AV3V lesion Dahl S rats received daily injections of either vasopressin (pitressin tannate, 500 mU/kg) or vehicle during 10 wk of 8% high-NaCl diet. Sham-lesioned rats served as controls. The blood pressure in sham-lesioned rats receiving vehicle was 189 mmHg after 10 wk of high-NaCl diet. Lesioned rats given vehicle showed a significantly smaller increase in blood pressure than sham-lesioned rats (P less than 0.001), the blood pressure averaging 161 mmHg at 10 wk. Lesioned rats given vasopressin also showed a smaller increase in blood pressure than sham-lesioned rats (P less than 0.05), but the final blood pressure averaged 176 mmHg and was significantly higher than that of lesioned rats given vehicle (P less than 0.025). Vasopressin injections corrected the hypernatremia in lesioned rats. In another experiment the effect of the AV3V lesion on the renal papillary plasma flow (RPPF) in Dahl S rats was studied. Dahl S rats have a lower RPPF than Dahl salt-resistant (R) rats even on a low-NaCl intake. The AV3V lesion increased the RPPF by 14% in S rats (P less than 0.025). These findings suggest that NaCl-induced hypertension in Dahl S rats requires the integrity of the AV3V region for its full expression, and the ability of the AV3V lesion to attenuate the NaCl-induced hypertension in Dahl S rats is partly related to the attenuation of vasopressin release. Moreover, the AV3V lesion partly corrected one of the characteristic features of Dahl S rats, the reduction in RPPF, when compared with Dahl R rats, with both strains on a low-NaCl intake.