Carbamazepine (CBZ) is a widely used anti-epileptic drug. One frequently observed side effect is hyponatremia which rarely develops into severe clinical symptoms. During the past years two hypotheses on the mode of action have been proposed: 1. Change in hypothalamic setpoint or osmosensing; 2. Targeting of renal salt and water transport. Until now no experimental animal data are available to test these hypotheses. We investigated the effect of 100mg CBZ/kg BW/d for 3 days and 50mg CBZ/kg BW/d for 7 days in conscious rats (n=7, respectively) in metabolic cages. Both treatments did not result in different plasma Na⁺ concentrations or hypervolemia if compared to controls. 100mg CBZ/kg BW/d resulted in reduced food consumption, reduced urine osmolality and a severe reduction in creatinine clearance. At the lower dose a significant increase in fractional renal Na⁺ excretion and a decreased fecal K⁺ excretion was observed. In parallel plasma K⁺ concentration increased. This indicates an effect of CBZ on epithelial Na⁺ and K⁺ transport. Interestingly plasma osmolality increased in these animals. This finding is not compatible with increased water absorption under these conditions, as observed in humans. In conclusion CBZ interferes with electrolyte and water metabolism but the present settings do not suffice to mimic CBZ induced hyponatremia/hypervolemia. Further studies with defined water load will be performed to elucidate the mechanisms of CBZ action in epithelia.