A number of studies have reported that oxidant stress reduces the activity of isolated Na À K ATPase and Ca 2 ATPase which are known to aect the cell membrane integrity. The aim of the study is to determine whether the administration of lisinopril is able to protect the membrane-bound enzyme levels in isolated guinea pig hearts and also ascertain whether or not a relationship exists between oxygen free radicals and membrane bound Na À K ATPase and Ca 2 ATPase. Forty guinea pig hearts were studied in an isolated Krebs±Henseleit solution-perfused Langendor cardiac model. In all groups cardioplegic arrest was achieved by administering St. Thomas' Hospital cardioplegic solution (STHCS). Group 1 (control, n 10) received only STHCS. Group 2 (n 10) were arrested with lisinopril (l mmol l À1 ) added STHCS. Group 3 (n 10) were pretreated with oral lisinopril (0 . 2 mg kg À1 twice a day) for 10 days and then arrested with STHCS. Group 4 were also pretreated with oral lisinopril (0 . 2 mg kg À1 twice a day for 10 days), arrested with STHCS and reperfused with lisinopril added to Krebs±Henseleit solution (l mmol l À1 ). Hearts were subjected to normothermic global ischaemia for 90 min and then reperfused at 378C. Pretreatment and addition of lisinopril in the reperfusion buer improved the levels of membrane-bound enzymes. When the treated groups were compared with control hearts, the best results were achieved in group 4. The Na À K and Ca 2 ATPase levels increased from 466 . 38+5 . 99 to 560 . 12+18 . 02 and 884 . 69+9 . 13 to 1287 . 71+13 . 01 nmolPi mg À1 protein h À1 respectively ( p 5 0 . 05). These results suggest that lisinopril protects the cell membrane integrity and lessens free radical-induced oxidant stress.