OBJECTIVE: The authors investigated the relationship between anxiety—a facet of the Revised NEO Personality Inventory dimension of neuroticism—and serotonin 5-HT1A receptor binding potential. METHOD: Positron emission tomography with [11C]WAY-100635 was used to estimate regional 5-HT1A binding potential in 19 healthy volunteers who completed the Revised NEO Personality Inventory. Correlation coefficients were calculated to determine the degree of association between 5-HT1A binding potential and personality inventory measures. RESULTS: There was a significant negative correlation between 5-HT1A binding potential and anxiety in four regions: the dorsolateral prefrontal cortex, anterior cingulate cortex, parietal cortex, and occipital cortex. CONCLUSIONS: The inverse relationship between 5-HT1A receptor binding potential and anxiety is consistent with 1) animal models that have shown higher anxiety in mice lacking 5-HT1A receptors and 2) clinical trial data that have demonstrated antianxiety properties of partial 5-HT1A agonists.