The blood pressure changes and behavior of vasoactive hormones after various stimuli were studied in eighteen patients with end-stage renal disease maintained on chronic hemodialysis. Group A patients (n = 9) were not subject to intra- or post-dialysis hypotensive episodes, and Group B (n = 9) frequently had such episodes. A 500 ml hypertonic saline infusion produced no change in blood pressure in either group, despite significant rise of vasopressin levels in both. Plasma renin activity levels were similar and became appropriately suppressed by the infusion in both groups, whereas norepinephrine rose significantly only in Group A, but not Group B where it was already higher at baseline. The regular dialysis session produced, as expected, a significantly more profound hypotensive effect in Group B, but was accompanied in both groups by decrease in vasopressin and increase in plasma renin activity. Norepinephrine change differed in the two groups: it decreased in Group A as expected from its capacity to be dialyzed, but rose in several hypotensive patients in Group B, indicating appropriate response to baroreceptor stimulation and leading to an unchanged average. These findings suggest that dialysis-induced hypotensive episodes are not necessarily associated with autonomic neuropathy or with abnormal patterns of vasopressor hormone response to stimuli. They also shed new light on the factors regulating vasopressin secretion under these circumstances, since they indicate that the osmoreceptor and/or sodium-sensitive receptor may be a more dominant mechanism in the regulation of vasopressin release than the volumetric mechanism responding to fluid volume changes.