Alterations of thyroid hormone indices have been described in patients with nephrotic syndrome. However, the majority of these patients also had either diabetes mellitus or significant renal failure, conditions known to alter thyroid hormone indices. To evaluate the changes in serum thyroid hormone indices due to nephrotic syndrome per se, we studied 15 nondiabetic patients with untreated nephrotic syndrome who had normal glomerular filtration rates (108 ± 5.3 ml/min). The serum levels of total thyroxine (TT4) were decreased in 7 of 15 patients with a mean of 5.7 ± 0.66 μg/dl (normal: 8.0 ± 0.14 μg/dl; p < 0.01). Serum levels of thyroxine-binding globulin were reduced in 2 of 6 patients and triiodothyronine (T3) uptake ratio values were elevated in 3 of 15 patients. Free T4 levels by radioimmunoassay and equilibrium dialysis were either normal or elevated. Both the basal serum thyroid-stimulating hormone (TSH) levels and the peak TSH response to thyrotropin-releasing hormone (TRH) were within the normal range. Serum levels of total T3 (TT3) were reduced in 8 of 15 patients (101 ± 12; normal 147 ± 2.8 ng/dl; p < 0.01) but those of total reverse T3 (TrT3) were normal. Free rT3 levels were elevated in 7 of the 10 patients studied. Patients with reduced serum levels of TT4 also had low TT3 values. The TT3/TT4 ratios were normal in these patients. There were direct and significant (p < 0.01) correlations between the total serum levels of both TT4 and TT3 and those of serum albumin. These data indicate that: (1) nephrotic syndrome per se is associated with alterations in thyroid hormone indices; (2) the normal free T4 levels, the normal TSH response to TRH and the normal TT3/TT4 ratios suggest that the production rates of T4 and T3 are not impaired; (3) the reduced serum levels of TT4 and TT3 in these patients may be due to decreased binding to and/or concentration of serum carrier proteins, and (4) as in acute and chronic renal failure, patients with nephrotic syndrome with normal renal function have normal total and increased free rT3 values in association with reduced TT3 levels. Since these three groups of patients have elevated blood levels of parathyroid hormone, it is tempting to speculate that excess parathyroid hormone may affect rT3 metabolism.