In order to examine differences in the atypical symptoms of depression between unipolar and bipolar patients, we studied 109 depressed patients (79 unipolar and 30 bipolar subjects) diagnosed with DSM-IV criteria. Patients were assessed using the Atypical Depression Diagnostic Scale (ADDS), a semi-structured interview that rates mood reactivity and other atypical depressive symptoms. Although atypical depression was common in this sample (28% of cases with definite atypical depression), no differences were found between the unipolar and bipolar patients in either the atypical symptom profile or the prevalence of an atypical depression diagnosis. The interrelationships between the atypical symptoms were also examined using a hierarchical cluster analysis. A five-cluster solution maximized differences between groups, with results suggesting that atypical depression may be a heterogeneous diagnosis.