The clinical features of Whipple's disease (WD) consist of arthropathy that precedes the involvement of other organs, such as the gastrointestinal tract, nervous system and heart. It has been shown that gastrointestinal manifestations can be precipitated by immunosuppressive therapy used to control the arthropathy. In the present study, we investigated the clinical features of the Italian population of patients affected by WD. The clinical histories of 22 patients with WD were reviewed. Relationship between previous treatments and onset of symptoms was analysed. 20/22 patients suffered from arthropathy that had started before gastrointestinal complaints; gastrointestinal symptoms were present in 18 patients and neurological involvement was found in 5. WD must always be taken into account in male patients with long-standing ill-defined arthropathy, and it should be ruled out before starting immunosuppressive or antibiotic treatment that can make correct diagnosis and management very difficult.