This paper examines the association between psychiatric disorders and headache syndromes in a longitudinal epidemiologic sample of young adults who were selected from the general population of Zurich, Switzerland. Headache syndromes were defined according to the newly introduced diagnostic criteria of the International Headache Society in 1988. The prevalence rates of psychiatric disorders, according to specific headache subtypes, were examined both cross-sectionally and longitudinally. In the cross-sectional data, migraine with aura was associated with hypomania, recurrent brief depression, and all of the anxiety disorders, whereas only the phobic disorders and panic were elevated among subjects with migraine without aura. Similar findings emerged for the longitudinal data, with the exception that major depression was associated with both subtypes of migraine. Subjects with tension-type headaches did not differ from controls with respect to any of the effective or anxiety disorders in both the cross-sectional and longitudinal data. Prospective study data indicated that the age of onset of anxiety disorders generally preceded that of migraine and that the onset of affective disorders in the majority of comorbid subjects followed that of the onset of migraine. In order to investigate the mechanism for the associations between anxiety/depression syndromes and migraine, patterns of co-transmission of migraine and anxiety/depression were examined in data from a controlled family history study of migraine. The results were consistent with a syndromic relationship between migraine and anxiety/depression, rather than their representing discrete manifestations of shared underlying etiology. The implications of these data for research and clinical work are discussed.