Twenty patients with serum levels of T4 and T3 within the normal range but with elevated serum concentrations of TSH were evaluated before and after treatment with L-T4. This therapy increased serum T4 (5.5 +/- 1.1 to 8.8 +/- 1.8 microgram/dl) and T3 (116 +/- 20 to 137 +/- 28 ng/dl) levels. Cardiac systolic time intervals (STI) were significantly (P less than 0.01) reduced by this therapy. The preejection period (123 +/- 18 to 114 +/- 14 msec; n = 12), the change in preejection period (+17 +/- 17 to +6 +/- 15 msec; n = 12), the ratio of preejection period to left ventricular ejection time (0.412 +/- 0.068 to 0.357 +/- 0.063 msec; n = 12), and the interval from the Q wave of the electrocardiogram to the pulse wave arrival time at the brachial artery (224 +/- 10 to 200 +/- 13 msec; n = 10) were consistently reduced. Cardiac STI were significantly correlated with serum TSH and T4 levels, but not with serum T3 levels. Normalization of serum TSH levels was associated with changes in QKd measurements even in those patients with minimal elevations in serum TSH. These studies demonstrate that patients having the combination of elevated TSH but T4 and T3 levels in the normal range have alterations in STI which can be changed significantly by L-T4 in doses which normalize TSH secretion. These data suggest that such patients have a mild form of primary hypothyroidism.