SUMMARY We studied the effects of anteroventral third ventricle (AV3V) lesions on the vascular Na + -pump activity of deoxycorticosterone acetate-salt (DOCA-salt) treated rats. Blood pressures and Na + -pump activity of the isolated tail arteries, measured as ouabain-sensitive w Rb + -uptake, were determined in untreated control rats, DOCA-salt treated rats, rats with AV3V lesions, and rats with AV3V lesions which were treated with DOCA-salt. Control rats receiving DOCA treatment developed higher blood pressures than rats receiving no DOCA treatment. Placement of AV3V lesions prior to administration of DOCA prevented the increase in blood pressure. Vascular Na + -pump activity in the DOCA-treated group was reduced by 20% compared to all other groups. The AV3V lesions prevented the suppression of Na + -pump activity caused by DOCA treatment. Suppression of vascular Na + -pump activity was due to a humoral substance since Na + -punip activity of tail arteries from control rats incubated in plasma from DOCA-salt treated rats was suppressed by 25% when compared to those incubated in control plasma. Our findings support the hypothesis that a circulating pressor substance is at least partially responsible for the development of DOCA-salt hypertension and that the mechanism by which AV3V lesions prevent DOCA hypertension may be through the interruption of secretion, transport, or synthesis of this factor. (Hypertension 4: 575-580, 1982) KKV WORDS • hypertension • blood pressure • Na + -pump activity • Rb-uptake • tail artery • AV3V lesion