Rats with a genetic susceptibility to salt hypertension were given repeated neonatal injections of guanethidine. Vascular reactivity and tissue catecholamine concentrations indicated that a peripheral sympathectomy had been produced. Chemically sympathectomized rats had lower blood pressure than controls while fed a diet containing 0.4% NaCl. Furthermore, the dramatic rise in blood pressure exhibited by control rats fed a diet containing 8.0% NaCl was completely absent in sympathectomized rats similarly fed. The absence of salt-induced hypertension was observed regardless of whether the animals were anesthetized with ether or pentobarbital or had the blood pressures determined in an unanesthetized state. Finally, two-kidney Goldblatt hypertension did develop in sympathectomized rats, but to a level below intact rats similarly treated.