Background: We investigated the relationship between low mood and challenging behaviour in people in the severe and profound range of intellectual disability, while controlling for the presence of potentially confounding variables such as diagnosis of autism, physical and sensory problems and ill health. Methods: The key workers of 52 people with severe and profound intellectual disability completed measures of depression, communication, challenging behaviour and provided information on relevant demographic and health variables. Results: Using the Mood, Interest and Pleasure Questionnaire for classification of mood, a significant difference was found between a "low mood" and "normothymic" group in the reported occurrence of challenging behaviour. This difference remained even when confounding variables such as the presence of autism, health and sensory difficulties were controlled. The frequency and severity of challenging behaviour was predicted by measures indicating the presence of low mood. Conclusion: People with severe and profound show clear and measurable signs of low mood, and in this relatively small sample of institutionalised individuals, low mood was associated with challenging behaviour.