Bipolar disorder often co-occurs with other axis I disorders, but little is known about the relationships between the clinical features of bipolar illness and these comorbid conditions. Therefore, the authors assessed comorbid lifetime and current axis I disorders in 288 patients with bipolar disorder and the relationships of these comorbid disorders to selected demographic and historical illness variables. They evaluated 288 outpatients with bipolar I or II disorder, using structured diagnostic interviews and clinician-administered and self-rated questionnaires to determine the diagnosis of bipolar disorder, comorbid axis I disorder diagnoses, and demographic and historical illness characteristics. One hundred eighty-seven (65%) of the patients with bipolar disorder also met DSM-IV criteria for at least one comorbid lifetime axis I disorder. More patients had comorbid anxiety disorders (N=78, 42%) and substance use disorders (N=78, 42%) than had eating disorders (N=9, 5%). There were no differences in comorbidity between patients with bipolar I and bipolar II disorder. Both lifetime axis I comorbidity and current axis I comorbidity were associated with earlier age at onset of affective symptoms and syndromal bipolar disorder. Current axis I comorbidity was associated with a history of development of both cycle acceleration and more severe episodes over time. Patients with bipolar disorder often have comorbid anxiety, substance use, and, to a lesser extent, eating disorders. Moreover, axis I comorbidity, especially current comorbidity, may be associated with an earlier age at onset and worsening course of bipolar illness. Further research into the prognostic and treatment response implications of axis I comorbidity in bipolar disorder is important and is in progress.