In humans, there is a significant decrease in serum T3 and increase in rT3 at different time points post-myocardial infarction (MI), whereas serum TSH and T4 remain unaltered. We report herein a time-course study of pituitary-thyroid function and thyroid hormone metabolism in rats subjected to MI by left coronary ligation (INF). INF- and SHAM- operated animals were followed by serial deiodination assays and thyroid function tests, just before and one, four, eight and twelve weeks after surgery. At 4 and 12 weeks post-infarction, liver D1 activity was significantly lower, confirming tissue hypothyroidism. D3 activity was robustly induced one week after INF only in the infarcted myocardium. Reminiscent of the consumptive hypothyroidism observed in patients with large D3-expressing tumors, this induction of cardiac D3 activity was associated with a fall in both serum T4 (50% decrease) and T3 (37% decrease) despite compensatory stimulation of the thyroid. Thyroid stimulation was documented by both hyperthyrotropinemia and radioiodine uptake. Serum TSH increased by 4.3-fold in the first and 3.1-fold in the fourth weeks (P<0.01), returning to the basal levels thereafter. Thyroid sodium/iodide-symporter (NIS) function increased one week post-INF, accompanying the increased serum TSH. We conclude that the acute decrease in serum T4 and T3 after INF is due to increased thyroid hormone catabolism from ectopic D3 expression in the heart.