The aim of the present study, was to establish the hepatic profile of acyl-coenzyme A (acyl-CoA) in relation to the hepatic profile of acylcarnitines in chronically hyperammonemic spf mice (hereditary deficiency in ornithine transcarbamylase) treated with sodium benzoate alone or in combination with L-carnitine. The muscular profile of the acylcarnitines and the stability of sarcolemma were also assessed in the same mice. Following administration of sodium benzoate, we observed decreases in hepatic total and free coenzyme A and in acetyl-CoA, which was accompanied by an increase in hepatic acyl-CoA. This treatment also resulted in increased free carnitine, decreased total carnitine, and decreased short and medium chain acylcarnitines in the liver. Increases in plasma creatine kinase levels, muscular free, total, and in short and medium chain acylcarnitines were also observed in this treatment group. In mice receiving a combination of sodium benzoate and L-carnitine, increases in free and total coenzyme A, acetyl-CoA and in free, total and esterified hepatic carnitines were observed. In this treatment group, the plasma level of creatine kinase was found to be reduced, while the free muscular carnitine was increased. Our results indicate that sodium benzoate is implicated in the decrease of total hepatic coenzyme A, through either an inhibition of CoA synthesis or activation of its degradation. The distribution of hepatic coenzyme-A and of hepatic and muscular carnitine (free or esterified) is altered following administration of sodium benzoate which results in a further destabilization of the sarcolemma induced by hyperammonemia. Supplemental treatment with L-carnitine was shown to have a positive effect by increasing hepatic coenzyme A and carnitine levels and restoring the stability of the sarcolemma caused by the treatment of sodium benzoate alone.