Spontaneously hypertensive rats (SHR) of the Okamoto strain exhibit a significant exacerbation in severity of hypertension when fed diets high in NaCl. To examine the hypothesis that abnormalities in the monoaminergic innervation of the hypothalamus and brainstem contribute to the NaCI-induced exacerbation of hypertension, the monoamine and monoamine metabolite contents of specific hypothalamic and brainstem regions thought to be involved in the pathogenesis of hypertension were determined in SHR fed a diet containing 8 % or 1 % NaCl for either 2 or 6 weeks beginning at age 8 weeks. SHR maintained on the 8% NaCl diet for 2 weeks displayed significant decreases in norepinephrine in both the anterior and posterior hypothalamic regions but not in other brainstem or hypothalamic regions, as compared with animals consuming 1% NaCl. In addition, stores of the principal terminal norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol were reduced in the anterior hypothalamic region of SHR fed an 8% NaCl diet for 2 weeks. After 6 weeks on the diets, SHR fed 8% NaCl showed small but statistically nonsignificant reductions in norepinephrine stores of the anterior hypothalamic region as compared with SHR fed a basal diet, while WKY fed 8% NaCl had significantly elevated norepinephrine stores in the anterior hypothalamic region as compared with WKY fed a basal diet. There was a significant group × diet interaction (p < 0.05). After 6 weeks on the 8% NaCl diet, SHR (but not WKY) displayed a significant reduction in norepinephrine content of the posterior hypothalamic region. No NaCI-induced differences in norepinephrine stores were found in the pons or medulla of either strain. No alterations in serotonin, dopamine, or epinephrine content were correlated with the differential rise in blood pressure following 8% NaCl feeding in SHR as compared with WKY. These results support the hypothesis that diets high in NaCl elevate blood pressure in NaCI-sensitive SHR by reducing noradrenergic input to depressor neurons in the hypothalamus. © 1987 American Heart Association, Inc.