Whipple's disease is a rare systemic infectious disease. To date, it has neither been possible to culture the bacillus Tropheryma whippelii, nor to infect other individuals with the pathogen. Today the diagnosis is confirmed by means of polymerase chain reaction (PCR) technology. Typically, the material for the PCR analysis comes from the duodenum. The diagnosis can also be established in this way on the basis of other tissue, or the cerebrospinal fluid. Treatment should only be carried out with antibiotics which cross into the cerebrospinal fluid, since there can also be an unrecognised involvement of the CNS. At present, the favoured method of treatment is the daily parenteral administration of 1.2 million units of benzylpenicillin (penicillin G) and streptomycin 1 g for a period of 2 weeks. This is followed by treatment with cotrimoxazole (trimethoprim 160 mg and sulfamethoxazole 800 mg) twice daily for 1 to 2 years. The treatment should begin and end with a PCR analysis of cerebrospinal fluid, in order to definitively diagnose infection of the CNS with Whipple's disease and to document the disappearance of the bacillus from the CNS.