We tested the effect of variation of intake of carbohydrate, fat, protein, and total calories on the metabolic rate and thyroid hormones in an 18-yr-old female with total acquired lipodystrophy and a 23-yr-old normal female control subject. The lipodystrophic subject's resting metabolic rates, when expressed as W/m² body surface area, were elevated and varied directly with the caloric intake. The metabolic rates were highest after 3 days of the protein-supplemented diet and lowest after a 3 day fast. Serum triiodothyronine (T₃) concentrations of the lipodystrophic subject were within the normal range but varied directly with the caloric content of the diet. T₃ was highest during the period of protein supplementation and lowest after the 3 day fast. The resting metabolic rate rose beyond the normal range in the control subject only after 3 days of the protein-supplemented diet and fell to low normal values after the 3 day fast. In contrast to the finding in the lipodystrophic subject, T₃ concentrations were stable after each 3–6 day dietary alteration. We conclude that there is relative metabolic lability in the lipodystrophic subject, and this may be related to the diminished capacity to store energy as fat. Metabolic rates, when calculated as W/kg estimated lean mass, were normal in the lipodystrophic subject, consuming reduced amounts of food (1800 cal/day). The role, if any, of T₃ in modulating these processes is unclear. The subject with lipodystrophy may demonstrate a form of dietary-induced thermogenesis.