Two cases of hypothyroidism with cardiac attack (acute myocardial infarction, AMI) following thyroxine replacement were reported. Neither of these cases showed any major coronary artery disease. The first case was a 58 year-old male who was treated with L-thyroxine (initial dose 0.025mg/day) for hypothyroidism due to Hashimoto's disease. The dose was increased up to 0.1mg/day within 2 weeks. Acute myocardial infarction occurred 6 weeks after the replacement was started. Angiographical study showed no notable pathological change in major coronary arteries, but echocardiography demonstrated diffuse hypokinesis of the left ventricular wall. The second case was a 61-year-old female who suffered from Graves' disease and had been treated with thiamazole (2.5mg/day) for 15 years. Later, she became hypothyroid and was treated with thyroxine. At first, 0.05mg/day of L-thyroxine was given, and then the dose was increased up to 0.1mg/day after the 7th week. Acute myocardial infarction occurred 3 weeks after the dose was increased. Angiographic study of the coronary arteries revealed no abnormality. Possible causes of AMI in thyroxine replacement were discussed in relation to vascular spasm and small vessel disease of the heart. Importance of echocardiographic study before hormone replacement therapy is stressed, particularly for middle/old-aged patients with long-term hypothyroidism.