Five patients with Whipple's disease all suffered from arthralgia for a long time (15 years in one case) before developing gastrointestinal or other symptoms. In all patients, arthralgia was seronegative, and there was no evidence of joint destruction. Arthralgias were symmetric and migrating. Whipple's disease is part of the differential diagnosis of enteropathic arthralgia. Thereby, the polymerase chain reaction can be a helpful tool to prove Whipple's disease in difficult differential diagnosis.