This paper demonstrates that the rhesus monkey provides an excellent model to study mechanisms underlying human anxiety and fear and emotion regulation. In previous studies with rhesus monkeys, stable, brain, endocrine, and behavioral characteristics related to individual differences in anxiety were found. It was suggested that, when extreme, these features characterize an anxious endophenotype and that these findings in the monkey are particularly relevant to understanding adaptive and maladaptive anxiety responses in humans. The monkey model is also relevant to understanding the development of human psychopathology. For example, children with extremely inhibited temperament are at increased risk to develop anxiety disorders, and these children have behavioral and biological alterations that are similar to those described in the monkey anxious endophenotype. It is likely that different aspects of the anxious endophenotype are mediated by the interactions of limbic, brain stem, and cortical regions. To understand the brain mechanisms underlying adaptive anxiety responses and their physiological concomitants, a series of studies in monkeys lesioning components of the neural circuitry (amygdala, central nucleus of the amygdala and orbitofrontal cortex) hypothesized to play a role are currently being performed. Initial findings suggest that the central nucleus of the amygdala modulates the expression of behavioral inhibition, a key feature of the endophenotype. In preliminary FDG positron emission tomography (PET) studies, functional linkages were established between the amygdala and prefrontal cortical regions that are associated with the activation of anxiety.