Abstract The prevalence of DSM-IV atypical depression and comparisons between atypical and typical depression were studied in 203 consecutive unipolar and bipolar depressed outpatients presenting for treatment of depression in private practice. The prevalence of atypical depression was 31%. Of the variables investigated (unipolar/bipolar diagnosis, age at baseline/onset of first major depressive episode, gender, psychosis, comorbidity, chronicity, duration of illness, recurrence, and severity), a bipolar II diagnosis was significantly more common, the age at baseline and duration of illness were significantly lower, and the proportion of females and psychiatric comorbidity were significantly higher in atypical versus typical depression. Secondary analysis showed that bipolar II atypical depression had a significantly earlier age at baseline/onset and affected more females, but there were no other significant differences versus typical depression. The findings suggest important clinical differences between atypical and typical depression, and a bipolar II subtype may be separated from the broad category of atypical depression.