An attempt has been made to establish the origin of the elevated serum creatine kinase which occurs in most patients with myxoedema. Parallel determinations of a number of other serum enzymes were made but the incidence of elevated values was appreciably less than in the case of creatine kinase. Rather surprisingly, the serum amylase activity was found to be increased in more than 50% of the patients studied. Creatine kinase isoenzymes were separated by starch-gel electrophoresis of the sera of 26 patients with myxoedema. In 25 the MM isoenzyme only could be identified while the remaining serum also contained a trace of the MB fraction. Similar isoenzyme studies were made with the sera of normal and thyroidectomized rats, all of which are shown to contain all three isoenzymes. (MM, MB and BB) irrespective of thyroid functional status. No consistent difference was apparent between the patterns exhibited by the thyroidectomized and control groups, and it was concluded that thyroidectomized rats cannot be regarded as a suitable experimental model for the study of this aspect of human hypothyroidism. It is suggested that enzyme release in myxoedema is a non-specific effect, possibly die to diminution in the ATP content of tissues generally. The greater incidence of creatine kinase elevation is probably due to the relatively high concentrations of this enzyme in skeletal muscle, the mass of which is much greater than that of any other tissue.