This study examined the latent structure of psychiatric disorders in a sample with a high prevalence of PTSD. A series of confirmatory factor analyses tested competing models for the covariation between Structured Clinical Interview for DSM-III-R diagnoses among 1,325 Vietnam veterans. The best-fitting solution was a 3-factor model that included two correlated internalizing factors: anxious-misery, defined by PTSD and major depression, and fear, defined by panic disorder/agoraphobia and obsessive-compulsive disorder. The third factor, externalizing, was defined by antisocial personality disorder, alcohol abuse/dependence, and drug abuse/dependence. Both substance-related disorders also showed significant, albeit smaller, cross-loadings on the anxious-misery factor. These findings shed new light on the structure of psychiatric comorbidity in a treatment-seeking sample characterized by high rates of PTSD.