The effect of hyperammonemia on plasma and urinary levels of carnitine was studied in different groups of +/Y (normal) and spf/Y (chronically hyperammonemic) mice. Experimental models of acute and subacute hyperammonemia were prepared in +/Y and spf/Y mice by the use of ammonium acetate ip injections and arginine-free diets, respectively. In acute hyperammonemia, the plasma levels of both free and acylcarnitines increased significantly whereas acyl/free carnitine ratio was decreased, indicating a mobilization of carnitine from the storage sites. The subacute hyperammonemia model showed the same tendency in respect of plasma and urinary carnitines; however, the values in plasma were more significantly different. The effect of sodium benzoate on plasma carnitine levels, during both an acute and a prolonged treatment, consisted in a significant lowering of free carnitine and a significant increase in the acyl/free carnitine ratio, in both +/Y normal and spf/Y mouse models. The changes in the urinary profile, on benzoate treatments, were not significant. These results demonstrate the individual effects of hyperammonemia and benzoate therapy on carnitine metabolism, which may be helpful in understanding and ameliorating the therapeutic approach to hereditary hyperammonemias.