The first aim of the present study was to determine the cause of dyspepsia after negative conventional diagnostic work-up. In such patients, an extended diagnostic work-up was performed including esophageal pH monitoring and manometry, gastric and hepatobiliary scintigraphy, and lactose tolerance test. In 88 of 220 dyspeptic patients (mean age 49 years, range 17-87; 114 women) presenting to our gastroenterological outpatient department, a cause for dyspepsia was found by conventional work-up. Thirty-one of the remaining patients did not enter extended work-up because of minor symptoms. In 47 of 101 patients entering extended work-up, a diagnosis was established (21 endoscopy-negative gastroesophageal reflux disease, 11 gastric stasis, 6 biliary dyskinesia, and 5 lactase deficiency among them). A second aim of the study was to determine whether clusters of symptoms such as "gastroesophageal reflux-like," "dysmotility-like," and "dyspepsia of unknown origin" reliably predict the groups of diseases suggested by these terms. This was not the case. In conclusion, in 40% of dyspeptic patients, a conventional diagnostic work-up led to a diagnosis that explained a patient's symptoms. After a negative conventional diagnostic work-up, an extended diagnostic work-up with functional tests yielded a possible explanation for their symptoms in 47% of patients. In such patients symptomatology was of little help for predicting the diagnosis.