To access the saliva level of free 3-methoxy-4-hydroxyphenylglycol (MHPG) as a biological index of anxiety disorders, gender- or age-dependent changes in saliva MHPG level in patients with anxiety disorders were investigated. Saliva MHPG levels in 196 normal volunteers (59 male, 137 female) and 42 outpatients with anxiety disorders (20 male, 22 female) at the initial consultation to the hospital were measured by gas chromatography-mass spectrometry. Saliva MHPG levels in patients were higher than those in normal subjects. The increase in saliva MHPG levels in male patients was greater than that in female patients. Age-associated increase in the saliva MHPG level was greater in patients than in normal subjects. Especially, a significant interaction of age vs. patient effect was found in female subjects (P=0.0005), but not in male subjects (P=0. 174). These data indicate that the measurement of saliva MHPG would be valuable for detecting pathological anxiety in male patients regardless of age and in older female patients, but not in younger female patients.