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The decreases in serum osmolality as well as the rate of ultrafiltration during hemodialysis and the influence of each upon the side effects of this treatment were studied in 13 chronic stable dialysis patients. Mannitol (9 mosm/kg water) was infused in two out of four dialyses, in a double blind fashion. A solution of 5% glucose in water was used as control. 1 week after the treatment, there was no residual mannitol in the patients’ serum (p < 0.0005). The decrease in osmolality during dialysis was lower when the patients received treatment with mannitol than with placebo: 14.7 versus 25.0 mosm/kg water (p < 0.001). The symptoms during dialysis were much less severe when the patients received mannitol (p < 0.05). Analyzed separately, ultrafiltration rate had no effect on severity of symptoms during dialysis (p > 0.1). Decrease in serum osmolality during dialysis seems to be the most important factor in the genesis of dialysis symptoms in chronic stable dialysis patients and are counteracted by the infusion of an osmotically active substance such as mannitol, 1 g/kg/dialysis; this results in a slight increase in body weight between dialyses, and cannot be used routinely because of slow accumulation.