OBJECTIVES: Oral candidiasis (OC) and oral hairy leukoplakia (OHL) are the most common oral mucosal diseases associated with HIV infection. Independent risk indicators associated with these sentinel opportunistic diseases have not been established in mixed race and gender adult populations in the southeast USA. The purposes of this study were 1) to estimate prevalence of OC and OHL among an HIV-1 positive adult population, and 2) to develop explanatory multivariable models for each disease outcome. METHODS: This cross-sectional study evaluated 631 adult dentate HIV-1 seropositive persons examined for HIV-associated oral mucosal diseases between 1995 and 2000 at University of North Carolina Hospitals in Chapel Hill, North Carolina using data collected from medical record review, interview questionnaire and clinical examination. We analyzed the data using t-tests, anova, and unconditional logistic regression. RESULTS: Prevalent OC was associated with low CD4+ cell count [<200 cells/microl, adj. OR = 12.7 (95%CI: 4.9-32.9)], antiretroviral combination therapy [OR = 0.6 (0.3-0.9)], and current smoking [OR = 2.5 (1.3-4.8)]. Prevalent OHL was associated with low CD4+ cell count [<200 cells/microl, OR = 7.2 (2.7-18.9)], antifungal medication use [OR = 1.8 (1.1-2.9)], current recreational drug use [OR = 2.5 (1.3-4.9)], and male gender [OR = 2.5 (1.3-4.8)]. CONCLUSIONS: While CD4+ cell count, and antiretroviral medication were important risk indicators for OC, and OHL, cigarette smoking appears to be an important risk indicator for OC in HIV-1-infected populations.