Adenosine administration was tested in rats with carbon tetrachloride-induced hepatic fibrosis and was able to partially prevent the enlargement of liver and spleen induced by the toxin. This amelioration of the hepatomegaly was accompanied by a 50% reduction of the liver collagen deposition and preservation of content of glycosaminoglycans. A stimulated hepatic collagenase activity is apparently the mechanism for reduction of collagen accumulation. These effects were associated with a striking improvement in liver function. Adenosine treatment did not modify the late hepatotoxic effect of the carbon tetrachloride; however, the stimulatory effect of the nucleoside on energy state appeared to counteract the drastic decreases in adenine nucleotides, ATP, ATP/ADP ratio and energy charge elicited by the hepatotoxin. Moreover, a possible beneficial action of enhanced hepatic oxygenation caused by the vasodilator properties of adenosine cannot be ruled out. Regardless of the mechanism, adenosine seems to change the cellular response to the injury induced by the hepatotoxin.