The assessment of psychological morbidity in patients with ALS has centered around depression, hopelessness, and anxiety. The Brief Symptom Inventory (BSI) offers an opportunity to explore psychological morbidity more broadly. We administered this instrument to 111 patients with ALS as part of a larger study of quality of life. Scores of ALS patients on the Global Severity Index and Positive Symptom Distress Index were comparable to the majority of distressed psychiatric outpatients and significantly higher than those of non-patient adults. Among BSI subscales, scores on the Anxiety, Depression, Phobic Anxiety, and Somatization subscales also were not significantly different from distressed adult psychiatric outpatients, and were greater than normal mean scores for a non-patient population sample. Based on these data, ALS patients appear to be significantly more distressed than non-patients in the identified areas, and as distressed as approximately 68% of a distressed psychiatric outpatient sample. In conclusion, a substantial number of individuals with ALS experience psychological distress of various types. Because psychological health impacts lifespan and quality of life in these individuals, broadly-based mental health assessment and treatment should remain an important part of care for patients with ALS. The effects of physical symptoms on responses to questions used to assess psychological distress must be considered.