OBJECTIVE: To use the rhesus monkey as a model to further characterize the behavioral and physiological correlates of extreme behvioral inhibition and to investigate the brain mechanisms underlying this trait. RESULTS Behavioral inhibition (BI) or, in its extreme form, freezing, is an adaptive response which individuals engage in when confronted with threatening situations. Clinical research has demonstrated that in its excessive form BI is a trait marker for children who are very shy and develop into overly fearful adolescents and adults. In addition, these individuals have increased adrenal-cortical and autonomic activity when tested in nonstressful conditions. Later in life, these individuals have an increased likelihood of developing clinically significant anxiety and depression suggesting that extreme behavioral inhibition may be an early marker for later development of psychopathology. Because of its potential clinical importance, we have developed a paradigm in rhesus monkeys to assess BI. As in human children, we have found that there is marked individual variability in the tendency to engage in BI and that this is a stable trait. We have characterized the biological correlates of extreme BI and found that these animals have relative right frontal electrical activity of elevated basal cortisol levels. The degree of frontal EEG asymmetry is stable within animals and is positively correlated with cortisol levels. These findings further characterize the endocrinology phenotype of fearful temperaments and point to mechanistic studies to further understand the biology of fear-related psychopathology. FUTURE DIRECTIONS Future studies are planned to further assay the role of neurochemical systems within the amygdala in mediating these responses. A continuation of the funding is currently being applied for. KEY WORDS benzodiazepine, neurobiology, development, fear, anxiety, cortisol, defense, behavior, brain, psychopathology