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OBJECTIVE: This study characterized the prevalence, characteristics, and impact of mental and general medical disabilities in the United States. METHOD: The 1994–1995 National Health Interview Survey of Disability was the largest disability survey ever conducted in the United States. A national sample was screened for disability, defined as limitation or inability to participate in a major life activity. Analyses compared cohorts who attributed their disability to physical, mental, or combined conditions. RESULTS: Of 106,573 adults, 1.1% reported functional disability from mental conditions, 4.8% from general medical conditions, and 1.2% from combined mental and general medical conditions. Disabilities attributed to a mental condition were predominantly associated with social and cognitive difficulties, those attributed to general medical conditions with physical limitations, and combined disabilities with deficits spanning multiple domains. In multivariate models, comorbid medical and mental conditions were associated with a twofold increase in odds of unemployment and a two-thirds increase in odds of support on disability payments compared to respondents with a single form of disability. More than half the nonworking disabled reported that economic, social, and job-based barriers contributed to their inability to work. One-fourth of working disabled people reported discrimination on the basis of their disability during the past 5 years. CONCLUSIONS: An estimated three million Americans (one-third of disabled people) reported that a mental condition contributes to their disability. Mental, general medical, and combined conditions are associated with unique patterns of functional impairment. Social and economic factors and job discrimination may exacerbate the functional impairments resulting from clinical syndromes.