BACKGROUND: Comprehensive health care is becoming an important issue; however, little is known about the complex relationships between perceived family support, self-rated health, and psychological distress in mixed middle-aged/older primary care patient samples. METHOD: In this cross-sectional and predominantly male sample of 137 patients attending their appointments at a primary care clinic in a Department of Veterans Affairs Medical Center, participants completed several questionnaires including the Family Adaptation, Partnership, Growth, Affection, and Resolve; the General Health Questionnaire-12; the Symptom Checklist-10; and the Primary Care Evaluation of Mental Disorders (PRIME-MD) screening questionnaire and interview. Data were collected in 1998. Eighteen percent of the participants were diagnosed with a mood disorder, and 15% were diagnosed with an anxiety disorder (PRIME-MD diagnoses). RESULTS: Perceived family support and self-rated health were negatively associated with psychological symptoms and certain psychological disorders, while perceived family support and self-rated health were positively rated. In addition, the interaction between perceived family support and self-rated health was significant (p <.01) in relating to psychological symptoms such that psychological symptoms were most elevated in participants reporting dissatisfying family support combined with poor self-rated health. However, the cross-sectional nature of the study prevents causal conclusions from being made. CONCLUSIONS: Physicians and other health care professionals are encouraged to assess both the perceived family support and self-rated health in an effort to conceptualize their patients' problems in a more comprehensive manner.