Lack of interest in sexual activity is one of the most prevalent psychosexual problems seen by clinicians. No consensus exists on etiology, symptomatology, appropriate therapeutic intervention, or prognosis. Desire disorders are believed to be highly refractory to treatment because of severe intrapsychic conflict, but no systematic data have been gathered about the histories of psychopathology in these individuals. Forty-six married subjects with a primary DSM-III diagnosis of global inhibited sexual desire (ISD) were compared with 36 matched controls on lifetime psychopathology, current psychological profiles, and premenstrual syndrome. A clinical interview, the Schedule for Affective Disorders and Schizophrenia-Lifetime Version and the SCL-90-R were administered to all subjects. Only ISD subjects free from any other axis I disorder, medical illness, medication use, or substance abuse were selected; controls met similar criteria but had no sexual dysfunction. Despite the fact that all ISD subjects had nearly normal psychological profiles at the time of assessment, more ISDs than controls had significantly elevated lifetime prevalence rates of affective disorder. The proportion of ISD individuals with histories of major and/or intermittent depression alone was almost twice as high as controls. Additionally, the initial episode of the depressive disorder almost always coincided with or preceded ISD onset. Significantly more ISD women than controls also had severe symptoms of premenstrual syndrome. The remarkable lifetime rate of affective illness in ISD patients suggests that there may be a common biological etiology or that affective psychopathology may be contributing to the pathogenesis of the ISD dysfunction.