Nonucler dyspepsia lacks a clear definition, and probably conceals several entities under this heading. It seems appropriate to deal separately with symptoms likely to be elicited from the upper digestive tract. Therefore, we propose "epigastric distress syndrome" (EDS) as a designation for chronic or recurrent epigastric pain without any anatomical antecedents and without concomitant symptoms consistent with established criteria of the irritable bowel syndrome. In this study 185 dyspeptic patients with a tentative diagnosis of EDS, based on symptoms and negative upper endoscopy, underwent laboratory screening, peroral cholecystograms, ultrasound scanning of the liver, biliary tract, and pancreas, biopsies from the distal part of the duodenum, and acid secretory tests. There were very few pathological findings. Five patients had gallstones. No single case of chronic pancreatitis or celiac disease was disclosed. Thus, EDS seems to be a "safe" diagnosis, and it is not unreasonable to assume that it could represent a disease entity. Although many patients had symptoms closely similar to those in duodenal ulcer, the mean basal and maximal acid output in this patient category did not differ from that observed among healthy subjects.