Changes in values for myoglobin, total creatine kinase (EC 2.7.3.2), and creatine kinase B-subunit in the serum of patients with thyroid disease are compared with values for these during the 24-h after myocardial infarction. Concentrations of all three of these muscle-derived proteins were significantly higher than normal in patients with primary hypothyroidism, and declined with treatment. Values for total creatine kinase activity were below-normal in hyperthyroid patients, but increased after treatment. Values for total creatine kinase and, to a lesser extent, myoglobin in hypothyroidism extend into the range of values observed after myocardial infarction. The mechanism of the changes in these analytes in hypothyroidism may be related to increased leakage from skeletal-muscle cells or diminished clearance from the circulation, or both.