This prospective study was designed to validate a novel biopsy urease test as well as a simplified 13C-urea breath test for the detection of Helicobacter pylori. In addition, the hypothesis was tested that both the reaction velocity of the urease test and the 13CO2 excess of the urea breath test may allow a prediction of the severity of gastritis. Seventy dyspeptic patients with unknown H. pylori status were included. The H. pylori status was assessed by means of culture and histology after Warthin and Starry stain. One antral and one body biopsy specimen were separately analyzed by the novel biopsy urease test (HUT). Also, a 13C-urea breath test using 75 mg 13C-labelled urea and orange juice as test meal was performed in all patients. Forty-seven patients (67%) were H. pylori positive as judged from histology and culture. In 46 patients, H. pylori infection was also detected by the novel biopsy urease test and by the urea breath test as well (sensitivity 97.9%). False-positive results were not observed by either method (specificity 100%). Both the reaction velocity of the urease test and the 13CO2 excess of the breath test significantly correlated with H. pylori density and grade and activity of gastritis. The determination coefficients, however, indicated that both methods allow a reliable prediction of the severity of gastritis only in about 40-50% of the patients. In conclusion, the novel biopsy urease test and the simplified 13C-urea breath test proved to be highly accurate in diagnosing H. pylori infection. Despite a significant correlation, neither the reaction velocity of the urease test nor the 13CO2 excess of the breath test are clinically useful for the prediction of the severity of gastritis.