The past 10 years have seen tremendous progress in the definition of the nuclear mechanism of action of thyroid hormones. Although the way in which these nuclear mechanisms underlie the 3,5,3'-triiodo-L-thyronine (T-3)-dependent stimulation of metabolic rate remains to be clarified, evidence favoring nonnuclear pathways is limited. Clearly, T-3 stimulates both the production and consumption of energy within cells, It also exerts a number of parallel effects that result in increased oxygen consumption, e.g. on mitochondrial structure and composition; on the metabolism of lipids, carbohydrates, and proteins, and on cardiac function. Additionally, T-3 may increase the proton permeability of the inner mitochondrial membrane, which implies that it may decrease the efficiency of energy production. These metabolic effects of T-3 appear to be restricted to homeothermic animals, representing a coordinated response to the challenge of maintaining body temperature.