Fifty-seven individuals with severe and profound mental retardation (18 with a DSM-IV diagnosis of depression, 19 with a Diagnostic Statistical Manual, 4th edition diagnosis of autism, and 20 who meet no criteria for an emotional disorder) were studied. The validity of the Diagnostic Assessment for the Severely Handicapped II depression subscale was evaluated to determine its value in categorizing individuals in these two groups. Suggestions were made for diagnosing depression in persons with severe and profound mental retardation. In a second study the above individuals were compared on symptomology to assess comorbidity with related symptoms. These "core," peripheral, or associated features of depression were identified. Implications of the findings for describing and defining depression in these persons are discussed.