A number of isolates of Saccharomyces cerevisiae have been associated with disease in immunocompromised individuals. Such isolates display a variety of characteristics that enable colonization and persistence in the host. The aim of the work presented here was to establish whether clinical isolates of S. cerevisiae were capable of adhering to epithelial tissue. Adherence to host tissue has been shown to be crucial to the virulence of the pathogenic yeast Candida albicans, and identification of this ability in S. cerevisiae might indicate a role for adherence in tissue colonization by this emerging pathogen. Clinical S. cerevisiae isolates were found to be capable of adhering to exfoliated buccal epithelial cells (BECs) but to a lesser degree than C. albicans. In contrast to the situation evident with C. albicans, the adherence of S. cerevisiae isolates to BECs was not influenced by the carbon source in which the yeast was grown. Treatment of S. cerevisiae with trypsin or proteinase K resulted in a significant reduction in adherence ability while adherence was unaffected by treatment of cells with mannosidase, thus indicating a possible role for proteins rather than mannoproteins in the adherence of S. cerevisiae to BECs.