Background The dialysis disequilibrium syndrome is characterized by neurologic deterioration and cerebral edema which occurs after hemodialysis. The purpose of this study was to investigate the pathogenesis of acute cerebral and pulmonary edema induced by hemodialysis. Methods We evaluated the effects of hemodialysis on the biochemical and hemodynamic parameters of the plasma and cerebrospinal fluid, including the intracranial pressure, dry/wet ratio, and pulmonary edema index, and we also examined the pathological changes of the brain and lung tissue in dogs suffering from uremia. Results Seventy-two hours after bilateral ureteral ligation, 10 uremic dogs were hemodialyzed for 2 hours, yielding a 73.6% and 60.1% decrease in the plasma urea and creatinine, respectively, a decrease in the plasma osmolality from (359 +/- 18) mOsm/kgH(2)O to (304 +/- 6) mOsm/kgH(2)O (P < 0.01), a decrease in the dry/wet ratio of the lung and brain tissue, and an increase in the hemodynamic parameters (right atrial pressure, right ventricular pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, and central venous pressure), intracranial pressure, total pulmonary resistance index, and pulmonary edema index. Moreover, the pathological examination revealed lung and brain edema in the dialyzed dogs. This group was compared to 3 control groups: 6 uremic dogs which were sham dialyzed without dialysate so that no fall in the plasma urea occurred, and 12 uremic and 12 nonuremic animals that were not dialyzed. However, the parameters mentioned above were not significantly changed among these 3 control groups. Conclusions The acute brain and lung edema in our model appeared to be primarily due to a large osmotic gradient between the plasma and the brain and lung. This is the "urea reverse effect" which promoted the osmotically-induced lung and brain swelling.