To understand the biologic significance of the low triiodothyronine (T3) syndrome in patients with chronic renal failure (CRF), we examined thyroid hormone profile, basal O2 uptake (VO2), and peripheral blood mononuclear leukocyte (PBL) ouabain binding in these patients and in the control subjects before and after L-triiodothyronine (T3) and sodium ipodate treatment. In the controls (N = 8), T3 administration increased serum total T3 from 136 +/- 15 to 232 +/- 11 ng/dl, and reduced total thyroxine (T4) from 8.14 +/- 0.56 to 6.08 +/- 0.43 micrograms/dl, free T4 from 1.59 +/- 0.12 to 1.03 +/- 0.05 ng/dl and thyroid-stimulating hormone (TSH) from 1.74 +/- 0.24 to 0.41 +/- 0.09 microU/ml. VO2 increased from 2.66 +/- 0.11 to 3.15 +/- 0.09 ml/kg/min. Ipodate treatment, on the other hand, resulted in a reduction of serum total T3 to 102 +/- 21 ng/dl, an increase in total T4 to 9.59 +/- 0.50 micrograms/dl, free T4 to 1.91 +/- 0.13 ng/dl and TSH to 3.64 +/- 1.14 microU/ml. VO2 decreased to 2.43 +/- 0.06 ml/kg/min. P values ranged from less than 0.05 to less than 0.001. In the CRF patients (N = 14), T3 treatment also resulted in a rise in serum total T3 from 75 +/- 5 to 185 +/- 8 ng/dl. Total T4 declined from 6.68 +/- 0.34 to 5.18 +/- 0.48 micrograms/dl, free T4 from 0.85 +/- 0.1 to 0.67 +/- 0.08 ng/dl and TSH from 3.67 +/- 0.86 to 0.94 +/- 0.3 microU/ml. VO2, however, did not change (from 2.91 +/- 0.12 to 2.99 +/- 0.17 ml/kg/min).(ABSTRACT TRUNCATED AT 250 WORDS)