Background: Despite retrospective reports of the onset of childhood bipolar disorder during the preschool period, few studies have investigated whether mania symptoms can be identified in preschoolers. A group of children with a cluster of mania symptoms that showed discriminant validity from other disruptive disorders was identified in a large preschool sample. These empirical data add to descriptive studies of mania in clinical preschool populations. An investigation of the characteristics of depression among putative bipolar preschoolers may inform the controversial nosologic questions that surround the diagnosis in this young age group. Method: This study, conducted from 2002 to 2007, investigated major depressive disorder (MDD) symptoms and severity in preschoolers with a bipolar syndrome in comparison to those with unipolar MDD, identified by an age-appropriate structured psychiatric interview, the Preschool Age Psychiatric Assessment (based on DSM-IV). Results: Twenty-one preschoolers were identified who met DSM-IV symptom criteria for bipolar I disorder and MDD and were compared to 54 preschoolers with unipolar MDD. The bipolar depressed preschoolers had significantly higher depression severity (p < .0001) and higher rates of comorbidity than did those with unipolar depression. The study is limited by the exploratory nature of clinical mania characteristics in preschoolers as well as reliance on parent reports of these symptoms. Conclusions: These findings suggest that, similar to adult bipolar patients, preschoolers with a putative bipolar syndrome experience clinically significant and severe depression. Symptom characteristics and comorbidity patterns also distinguished this group from the unipolar depressed preschoolers. Our findings underscore the marked depression that characterizes this putative bipolar syndrome and suggest that further investigation of this domain may clarify the nosology of this early-onset disorder.