For the past 50 years biomedical scientists have been in quest of an unidentified factor (hormone) that elevates blood pressure and regulates renal sodium transport, i.e., natriuretic hormone. Recent discoveries have led to the identification of such factors which are present in humans, rodents and amphibians, and which, in a complex manner, interact with each other and with the other regulatory systems. In experimental NaCl sensitive hypertension brain endogenous ouabain, via activation of renin-angiotensin system and of sympathetic nervous system, stimulates adrenocortical production of marinobufagenin, a natriuretic and a vasoconstrictor. The combined effects of these endogenous factors may account for the classical properties attributed by Dahl, deWardener and others to the hypothetical "natriuretic hormone".