The purpose of this study was to quantitate levels of cytokines in parotid saliva of subjects infected with human immunodeficiency virus-1 (HIV-1) and to determine if the cytokine profiles differ in subjects with an oral opportunistic infection, i.e., candidiasis or oral hairy leukoplakia. Parotid saliva samples were obtained from HIV-infected individuals with or without candidiasis or oral hairy leukoplakia and from healthy controls and were assessed by ELISA for levels of interleukin (IL)-1, IL-2, IL-4, IL-5, IL-10, transforming growth factor-β, tumor necrosis factor-α and interferon (IFN)-γ. Saliva from HIV-infected subjects with oral candidiasis had significantly higher levels of IFN-γ than that seen in HIV-infected individuals with no oral disease and significantly higher levels of IL-2, IL-5 and IFN-γ than saliva of healthy controls. No significant difference was seen in cytokine levels in saliva from HIV-infected subjects with no oral infections and healthy controls. The HIV-infected subjects with oral hairy leukoplakia displayed significantly higher levels of both IL-1α and IFN-γ compared with the HIV and no oral disease group and a higher level of IFN-γ than seen in saliva from the healthy control group. In comparing cytokine levels from both HIV and oral disease groups, significant differences were detected in levels of IL-5 and IL-10. These results indicate that the profile of salivary cytokines is altered as a result of the oral opportunistic infection candidiasis or oral hairy leukoplakia and also by concurrent HIV infection.