The role and regulation of (Na, K)-ATPase in cardiac sarcolemma are relatively well recognized today. Less abundant information is available about the time sequence of ischaemia-induced changes in activity and properties of the enzyme. In our experiments global ischaemia to the rat heart induces a time-dependent decrease in the activity and maximum velocity (Vm) value of sarcolemmal (Na, K)-ATPase. The depression of enzyme activity is fast and is expressed as early as 15 min after the onset of ischaemia. After 30 min of ischaemia the Vm decrease slows, probably due to an 'adaptational' decrease of the Km value of the (Na, K)-ATPase. This phenomenon may be interpreted as a mechanism by which the enzyme attempts to keep functioning in a situation when the supply by ATP is deficient. The depression in (Na, K)-ATPase activity is an early indicator of sarcolemmal damage. It outruns the changes in permeability of the cardiac sarcolemma to calcium and predicts ultrastructural damage to myocytes induced by ischaemia.