Two broadband latent factors—internalizing and externalizing—have frequently been identified in studies of the hierarchical structure of psychopathology. In the present research, 3 competing measurement models of putative internalizing disorders (i.e., a parsimonious single-factor model, a model based on the Diagnostic and Statistical Manual of Mental Disorders [4th ed., American Psychiatric Association, 1994], and an alternative model proposed by Krueger, 1999, and Watson, 2005) were evaluated in terms of their ability to account for lifetime patterns of diagnostic comorbidity. Four diagnostic assessments were performed on an age-based cohort of 816 persons over a 15-year interval. Each of the 3 measurement models demonstrated adequate or good fit to the data and similar approximating abilities. Additional analyses, however, suggested that nonspecific aspects of lifetime mood/anxiety or distress/fear disorders (i.e., general negative affect) largely accounted for indicators of psychosocial functioning at age 30 as well as densities of specific psychiatric disorders among the 1st-degree relatives of probands. The relevance of these findings for theoretical and descriptive models of internalizing disorders is discussed.