Prokinetic therapy has been shown to improve patients' symptoms associated with gastrointestinal motility disorders and quality of life. This study investigated the correlation between clinical improvement and quality of life after 12 months of treatment with cisapride or domperidone in patients with severe dyspepsia. Psychological and quality-of-life measures were assessed at baseline and after 12 months of therapy using three patient-administered, standardized questionnaires: the Minnesota Multiphasic Personality Inventory, the Millon Behavioral Health Inventory, and the Sickness Impact Profile. Changes in clinical symptoms were correlated with changes in these measures. Twenty-seven patients with symptoms of severe dyspepsia were treated with cisapride or domperidone (60-80 mg/day) for 12 months. Symptoms and quality-of-life measures were improved at the end of therapy. There were significant correlations between improvement in clinical symptoms and improvement in quality of life parameters. Patients with more marked symptom improvement had more significant improvements in quality of life measures. We conclude that prokinetic therapy improved symptoms and quality of life. Standardized questionnaires can be used to quantify response to prokinetic therapy and to individualize treatment regimens for patients with dyspepsia who have specific psychologic or behavioral characteristics.