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Although recent diagnostic systems support the distinctiveness of panic disorder (PD) and somatization disorder, a high level of comorbidity of these two diagnoses has been reported, indicating a need for investigations with external validators. One hundred fifty-nine outpatients with DSM-III-R PD and 76 surgical controls were screened for lifetime presence of DSM-III-R somatization disorder, and the risks for some types of psychiatric disorders in their families were computed. In our sample, 23% of women and 5% of men with PD also had DSM-III-R somatization disorder did not differ from women with PD only in age at onset of panic, agoraphobia, childhood history of separation anxiety, or lifetime diagnoses of other disorders. Familial risks for PD, PD-agoraphobia, and alcohol dependence were significantly higher for families of women with PD and women with PD plus somatization disorder than for controls. The familial risks for antisocial personality (ASP) disorder (a familial indicator for the somatization disorder spectrum of liability, phenomenologically independent from both PD and somatization disorder) were significantly higher for families of women with PD plus somatization disorder than for families of women with PD only or for controls. Application of DSM-IV criteria for somatization disorder substantially decreased the comorbidity with PD. Our data suggest that somatization disorder is not simply a form of PD, and that the two disorders may coexist in the same subject without sharing a common genetic diathesis. Compared with DSM-III-R, DSM-IV criteria for somatization disorder appear to be simpler in structure and of less complicated application.