To determine whether thirst mechanisms are altered in nondiabetic patients with chronic renal failure on hemodialysis, 4 patients with an average weight gain between dialysis sessions of more than 5 % of dry body weight (group I), 5 patients with less than 3 % weight gain (group II), and a group of 6 healthy subjects (group III) were submitted to infusion of hypertonic saline. After infusion the subjects had free access to water. Thirst was evaluated by visual analogue rating scales. Despite similar increments of effective plasma osmolality during saline infusion, patients of group I were thirstier than groups II and III (p < 0.005 and p < 0.01, respectively). Changes in thirst ratings were similar in groups II and III. Osmotic thresholds for thirst onset were similar in groups II and III (288.9 ± 8.5 and 289.8 ± 3.4 mosm/kg, respectively), but lower in group I (277.6 ± 7.6 mosm/kg). Nevertheless, great variations were observed in the latter group. Thus, 2 patients showed thresholds for thirst within the normal range, whereas the others had low osmolar thresholds for thirst and baseline plasma osmolalities and high basal thirst scores. During the drinking period, the patients of group I drank more (14.2 ± 2.8 ml/kg) than those of groups II (5.3 ± 1.6 ml/kg; p < 0.02) and III (10.2 ± 1.6 ml/kg; n.s.) The plasma levels of angiotensin II in uremic patients were higher than in healthy subjects, although there were no differences between groups I and II and no correlation between basal angiotensin II levels and the interdialytic weight gain. Our results indicate that some patients with chronic renal failure on hemodialysis manifest excessive thirst and gain more weight between dialysis sessions. This disturbance could be mediated by a resetting of the thirst osmostat, although an apparent cause of hyperdipsia was not evident in all patients.