The Kessler Screening Scale for Psychological Distress (K6; Kessler et al., 2002) has been used widely as a screener for mental health problems and as a measure of severity of impact of mental health problems. However, the applicability and utility of this measure for assessments within American Indian communities has not been explored. Data were drawn from a large-scale epidemiological study conducted in cooperation with 2 American Indian populations. Participants (N = 3,084) were 15-54 years of age and living on or near their home reservations; each completed an interview that included a version of the Composite International Diagnostic Interview (Robins, Wing, Wittchen, & Helzer, 1988) and the K6. A measure of both physical- and mental-health-related quality of life--the Medical Outcome Study's Short Form-36 (Ware & Sherbourne, 1992)--was used to examine the importance of the K6 over and above psychiatric diagnoses. The K6 was shown to be an appropriate screening and severity measure for mood disorders in these 2 samples. It also predicted health-related quality of life over and above that predicted by diagnoses alone. Inclusion of a measure such as the K6 as a complement to more traditional dichotomous diagnoses in both research and clinical practice is recommended. (Contains 4 figures and 3 tables.)