1. When all renal tissue is removed from salt-fed Dahl S rats, the excessive amounts of a circulating humoral vasoconstrictor effect (or lack of a vasodilator effect) are abolished, and Dahl S rats become the equal of Dahl R rats with regard to these circulating vasoconstrictor effects. 2. Total nephrectomy of salt-fed S rats also alters circulating humoral agents so that vasoconstrictor responses to sympathetic nerve stimulation and to noradrenaline infusions are markedly diminished in a perfused hindquarters preparation. 3. Both these effects of total nephrectomy are seen only in S rats, not in R rats, although plasma renin levels are lower in S rats. Thus total nephrectomy must remove much more renin and angiotensin II in R rats. 4. The effect of total nephrectomy in S rats need not necessarily be the direct removal of circulating vasoconstrictor humoral agents issuing from the S kidney. It is quite possible that removal of S kidneys has a strong influence upon the release of circulating vasconstrictor or vasodilator agents emerging from other parts of the body. 6. These effects of total nephrectomy occurring solely in S rats add still more evidence pointing to a pivotal role for the kidney in the mechanism of the NaCl hypertension of Dahl S rats.