Anxiety disorders are highly prevalent clinical conditions (25%) causing high number of hospital admissions and utilization of health care. Recent clinical trials indicate that gender differences in responsiveness to drug therapy also occur. Several lines of inquiry have focused on explaining this gender-related difference due to the higher prevalence of these disorders in women. There is a pile of evidence of a physiologic component is based on gender differences in gastrointestinal transit time, visceral sensitivity, central nervous system pain processing, and specific effects of estrogen and progesterone on gut function as well as on hypothalamic-pituitary-adrenal (HPA) circuitry in adult women., differences in autonomic nervous system, and reactivity. Decreased activity of HPA was observed in trait anxiety and anxiety disorders like panic disoerder or posttraumatic stress disorder. Twenty four patients high level of anxiety in general anxiety disorder participated in the study. ACTH and cortisol plasma concentrations were followed in regular intervals in patients who did not respond to 8 weeks of antidepressant treatment. Our findings show that highly anxious females exhibited lower cortisol release than highly anxious males, suggesting that high-anxiety in females may be associated with inability to respond to antidepressant treatment.