OBJECTIVE: The authors sought to derive heritability estimates for anorexia nervosa and to explore the etiology of the comorbid relationship between anorexia nervosa and major depression. METHOD: They applied bivariate structural equation modeling to a broad definition of anorexia nervosa and lifetime major depression as assessed in a population-based sample of 2,163 female twins. RESULTS: Anorexia nervosa was estimated to have a heritability of 58% (95% confidence interval=33%–84%). The authors were unable to completely rule out a contribution of shared environment. The comorbidity between anorexia nervosa and major depression is likely due to genetic factors that influence the risk for both disorders. CONCLUSIONS: Although the study was limited by the small number of affected twins, the results suggest that genetic factors significantly influence the risk for anorexia nervosa and substantially contribute to the observed comorbidity between anorexia nervosa and major depression.