OBJECTIVE: Comorbid bipolar and panic disorders aggregate in families. A phenotypic trait shared by both disorders is the sudden shift in affect observed in panic attacks and some rapid cycling states. The authors investigated whether comorbidity of bipolar disorder and panic disorder is associated with rapid mood switching in families with a high rate of bipolar disorder. METHOD: Six hundred six subjects with bipolar disorder from the NIMH Bipolar Disorder Genetics Initiative were included in the study. Logistic regression analysis was used to analyze rapid mood switching as a function of panic disorder diagnosis, sex, and familial risk for panic. RESULTS: Familial panic and the diagnosis of panic disorder in an individual subject increased the odds for rapid mood switching. The familial effect persisted when individuals with panic disorder were excluded from the analysis. CONCLUSIONS: Panic and rapid mood switching occurring together in familial bipolar disorder may define a useful subphenotype for future studies.