Left ventricular performance was studied in 15 patients with severe, primary hypothyroidism (mean serum total thyroxine of 0.8 μg per 100 ml and serum thyrotropin of 160 μU per milliter). Pretreatment systolic-time intervals were characterized by prolongation of the pre-ejection period (△PEP = +30) and reduction of the left ventricular ejection period (△LVET = -23) with a resultant increase in the PEP/LVET ratio (0.47). Nine of 14 patients demonstrated pericardial effusions. These abnormalities were reversed with physiologic thyroxine replacement. Further reductions of the △PEP and PEP/LVET ratio occurred with supraphysiologic doses (200 to 300 μg per day). During therapy, △PEP was inversely correlated with serum thyroxine (P<0.001) and directly correlated with serum thyrotropin (P<0.001). Thus physiologic thyroid hormone replacement, appropriately adjusted to need, appears necessary in hypothyroidism for optimal left ventricular function. (N Engl J Med 296:1–6, 1977) Severe hypothyroidism has long been known to produce abnormalities of cardiac structure and function.1 2 3 Studies in human subjects have documented reduced cardiac output,45 pericardial effusions6 7 8 9 10 11 and cardiomegaly.1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Animal studies have suggested that this decreased cardiac output may be related to abnormalities of myocardial contractility. Diminished peak tension and rate of tension development have been demonstrated in hypothyroid animals, opposite changes being present with induced hyperthyroidism.1617 Several recent noninvasive studies of myocardial function in human beings have demonstrated alterations in systolic-time intervals in hypothyroid and hyperthyroid patients and the reversal of these abnormalities after correction of the serum thyroid hormone concentrations.