The influence of thyroid hormone administration (daily doses of 0.1 mg of 3,3',5-triiodothyranine (T3)/kg for 1-3 consecutive days) on rat liver protein oxidation was investigated in relation to the calorigenic and lipid peroxidative actions of the hormone. T3 treatment elicited a progressive enhancement in the serum levels of the hormone, the rectal temperature of the animals, and in the rate of O2 uptake of the liver, changes that are significantly correlated and evidence the development of thyroid calorigenesis. Liver lipid peroxidation was augmented by T3 administration as determined by the tissue content of thiobarbituric acid reactants, with a maximal effect (3.1-fold increase) being found at 2 days after treatment, whereas protein oxidation measured by the content of protein hydrazone derivatives exhibited a maximal 88% increase at 3 days. Maximal rates of lipid peroxidation occur at 1 day after the administration of T3, whereas those of protein oxidation are attained after treatment with three daily doses of T3, time at which the former levels off. It is concluded that T3 administration induces a substantial enhancement in hepatic protein oxidation, in addition to lipid peroxidation, that seems to be due to the higher oxidative stress status conditioned in the liver by thyroid calorigenesis. Both processes exhibit a differential time course of changes, that may represent differences in the susceptibility of target molecules to free radical attack and/or in the efficiency of repair mechanisms.