Previous studies on the comorbidity of Obsessive-Compulsive Disorder (OCD) have largely focused on comorbidity with major depressive and anxiety disorders. The present investigation deals with a more complex pattern of comorbidity involving bipolarity. Indeed, in a consecutive series of 315 OCD outpatients, 15.7% had such comorbidity (mostly with bipolar II disorder). Unlike non-bipolar OCD patients, these had a more gradual onset of their OCD which, nonetheless, pursued a more episodic course with a greater number of concurrent major depressive episodes. These bipolar OCD patients had a significantly higher rate of sexual and religious obsessions, and a significantly lower rate of checking rituals. OCD probands with non-bipolar major depressive comorbidity (34.8%) were then compared with the remainder of OCD. These 'unipolar' OCD were older, had a more chronic course with hospitalizations and suicide attempts, had greater comorbidity with generalized anxiety disorder and caffeine abuse; finally, they were more likely to have aggressive obsessions and those with a philosophical, superstitious or bizarre content. Our data suggest that when comorbidity occurs with bipolar and unipolar affective disorders it has a differential impact on the clinical characteristics, comorbidity and course of OCD. We submit that the presence of major depression in OCD is incidental, as OCD in such cases dominates the course and dictates treatment choice. By contrast, when bipolar and obsessive-compulsive disorders co-exist, bipolarity should take precedence in diagnosis, course and treatment considerations.