Denture stomatitis (DS) is an inflammatory oral condition affecting most frequently the palatal mucosa covered by the fitting surface of a denture. The aim of this study was to determine the local cytokine profile generated in DS, as well as the level and identity of Candida involved. Palatal inflammation was determined by clinical indices in 93 upper denture-wearing subjects (42 with DS). The level of selected cytokines in palatal fluid was measured by cytometric bead array. Grouping of the cytokines associated with Th1, Th2, Th17 and regulatory T cell (Treg) responses, showed significant increases particularly for Th1 and Th17 responses. Using imprint culture, Candida was isolated from 48 patients (29 with DS). DS patients had significantly higher numbers of Candida isolated from the fitting surface of the denture (P=0.0113). However, there was significantly (P=0.03) higher numbers of Candida on the palate of non-DS patients. In summary, it would appear that an appropriate immune response is elicited in DS patients and whilst this appears to reduce Candida levels on inflamed mucosa, it is probable that Candida on the fitting surface of the denture remain protected from local immune responses which results in a continued reservoir of infection.