We used data from 3372 pairs of male twins from the Vietnam Era Twin Registry to examine comorbidity and familial influences on the frequently observed association between agoraphobic behavior and panic. Due to low prevalence of DSM-III-R-defined panic disorder, we also examined subjects who had experienced at least one panic attack during their lives. Agoraphobic behavior among individuals with a history of panic attacks showed familial aggregation (odds ratio = 5.7; P = .018 ). Probands with panic attacks and agoraphobic behavior and their co-twins had higher risk of major depression than probands without agoraphobic avoidance and their co-twins (P = .01). Groups did not differ for alcohol dependence or antisocial personality. Agoraphobic behavior associated with panic attack is familial and associated with comorbid major depression. Agoraphobia following panic attack does not seem to reflect severity as agoraphobic behavior in the proband was unrelated to risk of panic attacks in the co-twin.