Clostridium difficile is an important nosocomial pathogen, resulting in antibiotic-associated disease ranging from mild diarrhoea to the life-threatening pseudomembranous colitis. Upon antibiotic exposure, it is believed that the normal bowel microflora of patients is disrupted, allowing C. difficile to proliferate. Significantly, C. difficile is among only a few bacteria able to ferment tyrosine to p-cresol, a phenolic compound that is toxic to other microbes via its ability to interfere with metabolism. Therefore, the ability of different C. difficile strains to produce and tolerate p-cresol may play an important role in the development and severity of C. difficile-associated disease. In this study, it was demonstrated that two C. difficile hypervirulent 027 strains (Stoke Mandeville and BI-16) are more tolerant to p-cresol than other C. difficile strains including 630, CF4 and CD196. Surprising, it was shown that Clostridium sordellii also has a high tolerance to p-cresol, suggesting an overlap in the tolerance pathways in these clostridial species.