This study was a pilot investigation of risk factors for the development of Clostridium difficile toxin-associated diarrhoea and in particular the differential influence of antimicrobial agents. The study was a retrospective case-control design conducted at Freeman Hospital, Newcastle upon Tyne. Cases were inpatients with stool positive C. difficile toxin diarrhoea and two controls were drawn for each case matched for age (+/- 5 years) and type of admission (emergency or elective). Using conditional logistic regression analysis, cephalosporins and erythromycin were found to be statistically significantly associated with Clostridium difficile toxin associated-diarrhoea. The results form the basis for designing a larger, prospective study.