In two patients with multiple myeloma, men aged 72 and 54 years, diarrhoea developed upon chemotherapy with vincristin, doxorubicin and dexamethasone (VAD). In the second patient, diarrhoea developed after subsequent peripheral stem cell mobilisation. Pseudomembranous colitis was seen in the first patient during endoscopy but an enzyme immunoassay of the faeces was false negative for Clostridium difficile enterotoxin. The bacterium was later cultured from stool samples and toxins were detected in a repeated immunoassay. Stool samples of the second patient were positive for C. difficile enterotoxin. For both patients an antibiotic treatment resulted in a rapid recovery. In haemato-oncological patients, diarrhoea is often caused by oncolytic therapy. However, consideration should also be given to C. difficile infection as an alternative cause which is easily treatable.