The present study has been performed to test for ion release from isolated perfused rat liver exposed to hypotonic perfusates. Replacement of 40 mmol/l NaCl in perfusate by 80 mmol/l raffinose leads to slight alkalinization and slight decrease of liver weight. Subsequent decrease of perfusate osmolarity by omission of raffinose results in an increase of liver weight and a parallel increase of effluent sodium, chloride and potassium activity pointing to net uptake of solute free water. While effluent chloride and sodium activities approach perfusate activities within less than 2 min, a second, 6 min lasting increase of effluent potassium activity is observed, pointing to potassium release by the liver. This transient increase of effluent potassium activity is paralleled by a decrease of liver weight. Throughout exposure to hypotonic perfusates, lactate, pyruvate and glucose release by the liver is significantly decreased and effluent pH is rendered alkaline. Readdition of 80 mmol/l raffinose leads to rapid decrease of liver weight and a parallel decrease of effluent sodium, chloride and potassium activities followed by a 10-20 min lasting decrease of effluent potassium activity, pointing to net uptake of potassium, which almost matches the net release observed before. The transient decrease of potassium activity is paralleled by an increase of liver weight, an increase of effluent glucose, lactate and pyruvate concentration and an acidification of the effluent. Similar decrease of effluent potassium activity, acidification of effluent and increase of effluent glucose, lactate and pyruvate concentration are observed, if perfusates are made hypertonic by addition of raffinose.(ABSTRACT TRUNCATED AT 250 WORDS)