Abstract A significantly higher proportion of patients with headache showed scores in the psychopathological range of the General Health Questionnaire (GHQ) compared with controls, with ratings particularly high on the anxiety and depression subscales. Across the whole group, there was a significant negative correlation between platelet monoamine oxidase (MAO) activity and GHQ score overall, and with the anxiety and depression subscales. There was a significant positive correlation between platelet MAO activity and urinary output of the endogenous MAO inhibitor, tribulin. Within the migraine group, there was a significant negative correlation between tribulin output and GHQ score. These findings suggest that the biochemical nature of the anxiety associated with migraine may differ from that in other conditions such as generalized anxiety disorder where high platelet MAO activity and high tribulin output have been reported.