Background/Aims: Angiotensin II promotes sodium retention and influences the central regulation of fluid intake. Clinical studies on the effect of an angiotensin-converting enzyme inhibitor (ACEI) on xerostomia and thirst in chronic hemodialysis (HD) patients were scarce and gave contradictory results. We hypothesized that a more effective inhibition of the renin-angiotensin-aldosterone axis with the combined ACEI and angiotensin receptor antagonist administration may reduce thirst and xerostomia,thereby decreasing interdialytic weight gain (IWG) in HD patients. Methods: Twenty-one chronic HD patients (16 men, 5 women, mean age 54 ± 13 years, time on dialysis 50 ± 58 months) who had been on chronic ACEI therapy were studied. In a double-blind, crossover study, all subjects received in a random order either losartan (50 mg/day) or placebo for two 4-week periods with a 7-day wash-out. Basic biochemistry, serum electrolytes, plasma aldosterone, measurements of salivary flow rate after stimulation with paraffin chewing, and subjective xerostomia and thirst questionnaires were collected before dialysis sessions both before and after each treatment period. IWG and blood pressure were assessed at each dialysis. Results: The volume of saliva increased after losartan (from 1.2 ± 0.7 to 1.5 ± 1.0 ml/min, respectively; p = 0.03), but this was reflected neither by the severity of the symptoms of xerostomia assessed by the patients on a visual analog scale (31 ± 9 vs. 31 ± 8 mm, respectively) nor by the intensity of thirst (final score 22 ± 5 vs. 21 ± 5 at baseline). No changes of the mean IWG were observed during the treatment with losartan (2.5 ± 0.6 kg before and 2.4 ± 0.8 kg at the end of the treatment). Plasma aldosterone decreased at the end of the losartan therapy (from 151 ± 86 to 111 ± 51 pg/ml; p = 0.02). Predialysis serum potassium did not change during the study. Conclusions: The addition of an angiotensin receptor blocker to chronic ACEI therapy is not effective in reducing thirst and thereby IWG in chronic HD patients.