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Background Results from studies in serotonin-1A (5-HT 1A ) knockout mice and previous positron emission tomography (PET) studies in humans imply a role for 5-HT 1A receptors in normal state anxiety as well as in certain anxiety disorders. The objective of this study was to investigate 5-HT 1A receptor binding potential (BP) in social anxiety disorder (SAD). Methods Using PET and [carbonyl- 11 C]WAY-100635, we compared a homogeneous group of 12 unmedicated, male SAD patients with 18 healthy control subjects (HC). A multivariate ANOVA with all regional BP values as dependent variables, age and four radiochemical variables as covariates was performed. Results We found a significantly lower 5-HT 1A BP in several limbic and paralimbic areas but not in the hippocampus (p = .234) of SAD patients. The difference in 5-HT 1A binding was most significant in the amygdala (−21.4%; p=.003). There was also a more than 20% lower 5-HT 1A BP of SAD patients in the anterior cingulate cortex (p = .004), insula (p = .003), and dorsal raphe nuclei (p = .030). Conclusions The lower 5-HT 1A binding in the amygdala and mesiofrontal areas of SAD patients is consistent with 1) preclinical findings of elevated anxiety in 5-HT 1A knockout mice, 2) a previous PET study in healthy volunteers showing an inverse correlation between 5-HT 1A BP and state anxiety, and 3) another human PET study in patients with panic disorder showing reduced 5-HT 1A binding, thus corroborating the potential validity of 5-HT 1A receptors as targets in the treatment of human anxiety disorders.