Changes in blood volume are capable of altering the relationship between plasma osmolality (Posmol) and plasma arginine vasopressin (PAVP), presumably via a reflex elicited from cardiovascular receptors, but the precise location of the receptors involved in this response has not been established. Because cardiac receptors are capable of influencing AVP secretion, their specific effect was examined by producing volume changes in cardiac-denervated (CD) dogs and comparing the Posmol-PAVP relationship in these dogs with data from comparable experiments on sham-operated control dogs (cardiac-sham, CS). Posmol was increased by water deprivation for 96 h (volume depletion) and also by administration of hypertonic saline for 2 h (volume expansion). The slope of the regression line describing the Posmol-PAVP relationship in CS control dogs was steeper (P less than 0.01) during volume depletion (0.390) than it was during volume expansion (0.228), thus suggesting that volume depletion had enhanced and volume expansion had inhibited the secretion of AVP. In contrast, the slope of the regression line delineating the Posmol-PAVP relationship in CD dogs was essentially the same during volume depletion (0.288) as it was during volume expansion (0.291). It would seem that most, if not all, of the volume influences on the Posmol-PAVP relationship are mediated via reflex effects elicited by cardiac receptors.