Central nervous system (CNS) thyrotropin-releasing hormone (TRH) activity is of interest in patients with anorexia nervosa. First, anorexics have peripheral thyroid abnormalities that appear to be related to weight and nutritional status. Second, CNS TRH activity may effect many other physiologic systems that are known to be disturbed in patients with anorexia nervosa. We found that anorexic patients, when both underweight and studied after attaining goal weight, had significantly reduced CSF TRH concentrations in comparison to controls. These data suggest that weight gain or increased caloric intake, in contrast to its large effect on peripheral thyroid function, has relatively little effect on CNS TRH activity. The reason for reduced CSF TRH in goal weight anorexics is not known but could be trait related, a persistent defect slow to normalize after weight gain, or related to these patients still being at a weight lower than controls. Finally, in terms of CSF TRH concentrations, this study suggests that anorexia nervosa has a different pathophysiology than major depressive disorder.