Due to the systemic nature of Whipple's disease the clinical presentation may be highly variable. The diagnosis may therefore be unduly delayed. If untreated, Whipple's disease is still potentially lethal. In contrast, the endoscopic findings as they are observed in the postbulbar small intestine and the light microscopic picture of small intestinal biopsies are almost pathognomonic. Out of a group of 18 patients (14 male, 4 female, mean age = 45 yrs), 12 patients were diagnosed using upper gastrointestinal endoscopy and duodenal biopsy, while six patients were diagnosed only by a small intestinal capsule biopsy. The clinical history prior to diagnosis lasted from 1 m to 22 yrs (mean = 3 yrs 6 m) in the first group and from 4 yrs to 21 yrs (mean = 12 yrs 6 m) in the second group. The endoscopic findings at the time of diagnosis were: oesophagitis (1/12), erosive gastritis (4/12), atrophic gastritis (2/12), severe erosive bulbitis (3/10), pathognomonic post-bulbar duodenal lesions (9/12). In 20% of the patients the endoscopic lesions had disappeared 6 m after antibiotics while the lesions had disappeared in all cases 9 m after therapy, despite the fact that PAS positive macrophages remained present in the endoscopic biopsies for years. All patients were treated with antibiotics (8 tetracycline alone, 4 tetracycline, streptomycin and penicillin, 6 trimethoprim). Five patients (27%-4 of the tetracycline group) relapsed within 2 to 20 yrs after the initial diagnosis. Three of these patients (3/5) had typical duodenal lesions on endoscopy at that time.