To examine the role of the sympathetic nervous system in the development of deoxycorticosterone acetate (DOCA)/NaCl hypertension and to test the hypothesis that the responsiveness of the sympathetic nervous system to stress is enhanced during the developmental phase of hypertension in this model before resting sympathetic activity becomes increased, DOCA/NaCl-treated rats and uninephrectomized control animals were studied after 3, 7, 14, and 28 days of treatment. Basal plasma norepinephrine and epinephrine in conscious, unrestrained resting DOCA/NaCl-treated rats were the same as in controls at 3, 7, and 14 days but were significantly elevated at 28 days of treatment. Ganglionic blockade resulted in a significantly greater decrease in mean arterial pressure in DOCA/NaCl rats than in controls at 14 and 28 days of treatment. At 14 days, DOCA/NaCl rats exhibited significantly greater increments in plasma norepinephrine and epinephrine following cold stress than did H2O controls. Basal plasma prolactin levels were elevated and release of dopamine from isolated superfused mediobasal hypothalami reduced in 28-day DOCA/NaCl hypertensive rats. These results indicate that sympathetic nervous system activity increases progressively during the development of DOCA/NaCl hypertension and that the sympathoadrenal system is hyperresponsive to environmental stress even early in the course of DOCA/NaCl treatment and suggest that hypothalamo-hypophyseal function is altered in this model of hypertension.