The acute effect of a single intraperitoneal dose of alcohol (2 g kg-1 body weight) was studied in normally fed rats anaesthetised with sodium pentabarbitone . Rapidly achieved high blood alcohol levels were accompanied by an equally rapid but transient 4-fold increase in the total creatine kinase (CK) activity in the arterial plasma of animals of both sexes. Resting CK activity was significantly lower in female animals and although the magnitude of the alcohol-induced CK increase was the same in both sexes, the duration of the response was shorter in female rats. Electrophoresis showed the skeletal muscle-associated MM isoenzyme of CK to be predominant in resting plasma and also to account solely for the alcohol-induced increase in total CK activity. These results indicate that alcohol has a direct toxic action on skeletal muscle, causing transient loss of cellular integrity which permits the leakage of normally intracellular enzymes into the circulation.