Changes in weight, thyroid hormones and mood were examined in 15 obese (113 kg) women over an 18-week period. After 4 weeks of a 1200 kcal/day diet, patients were randomly assigned to one of two dietary conditions: very low calorie diet (VLCD) (n = 8) or balanced deficit diet (BDD) (n = 7). VLCD patients consumed 400 kcal/day for 8 weeks and then gradually returned to a 1200 kcal/day diet. BDD patients consumed 1200 kcal/day for the entire 18 weeks. Differences in weight losses between the conditions were statistically significant only during the consumption of the VLCD. Serum T3 decreased by as much as 66 percent in VLCD patients during consumption of the 400 kcal/day diet, whereas rT3 increased by as much as 27 percent. T3 increased when patients were realimented with a 1000 kcal/day balanced diet but remained a significant 22 percent below baseline at the end of the study. BDD patients also showed marked reductions in T3, as great as 40 percent, so that the differences between the two conditions were not statistically significant. Multiple regression analyses, collapsing across conditions (n = 15), indicated that weight loss at week 12 and baseline T3 accounted for 63 percent of the variance in the change in T3 at week 12. Patients in both conditions showed improvements in mood. Changes in depression were not associated with changes in serum T3.