Left ventricular performance was studied in 15 patients with severe, primary hypothyroidism (mean serum total thyroxine of 0.8 mug per 100 ml and serum thyrotropin of 160 muU per milliliter). Pretreatment systolic-time intervals were characterized by prolongation of the pre-ejection period (delta PEP = +30) and reduction of the left ventricular ejection period (delta 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 delta PEP and PEP/LVET ratio occurred with supraphysiologic doses (200 to 300 mug per day). During therapy, delta PEP was inversely correlated with serum thyroxine (P less than 0.001) and directly correlated with serum thyrotropin (P less than 0.001). Thus physiologic thyroid hormone replacement, appropriately adjusted to need, appears necessary in hypothyroidism for optimal left ventricular function.