The authors investigated cancer patients' interpretations of their physical symptoms and their illness beliefs with the objective of establishing the importance of these variables in predicting distress during chemotherapy treatment. Past researchers have suggested that causal attributions of physical symptoms and beliefs about illness progression and its consequences may serve as important mediators between number and perceived severity of symptoms and psychological adjustment in cancer patients during the treatment phase. Our aim in this study was to further these findings using the Self-Regulation Model as a theoretical framework. The study was cross-sectional in design, testing 72 patients with cancer receiving intravenous chemotherapy as outpatients in the United Kingdom. The participants completed questionnaires measuring number and perceived severity of symptoms, the causal attributions of these, illness and treatment beliefs, anxiety, and depression. The results showed that consequence beliefs serve as important mediators between number of symptoms and distress, explaining 15% of the variance in anxious mood and 5% of the variance in depressed mood. The authors found perceived severity of symptoms to be an independent predictor of anxious mood, explaining 7% of the variance. Its role in predicting depressed mood was not significant.