The aim of this study was to examine the outcome and comorbidity of patients with bipolar disorder presenting with first-episode as compared with multiple-episode mania. Based on studies from the prepharmacological era and the sensitization model of bipolar disorder, we hypothesized that compared with multiple-episode mania, first-episode mania would be associated with better outcome, milder severity, and less psychiatric comorbidity. Seventy-one hospitalized patients, age 12 years and older and meeting DSM-III-R criteria for bipolar disorder, were recruited over a 1-year period. Thirty-four (48%) first-episode and 37 (56%) multiple-episode patients were compared regarding demographics, phenomenology, comorbidity, family history, and short-term course. Compared with multiple-episode mania, first-episode mania was associated with significantly shorter hospitalization and a higher rate of comorbid impulse control disorders. These data provide indirect support for the sensitization model of bipolar disorder.