Joint occurrence of two or more diseases may impact their transmission, clinical presentation, management approaches, and treatment efficacy. Although oral candidiasis (OC) and oral hairy leukoplakia (OHL) are the most commonly occurring opportunistic oral diseases of HIV-infected patients, literature describing their joint occurrence is sparse. The purpose of this project was to develop an explanatory multivariable model for joint occurrence of OC and OHL (OC-OHL). This cross-sectional study examined 631 adult dentate HIV-1 seropositive persons for OC and OHL from 1995-2000 at the University of North Carolina Hospitals in Chapel Hill, NC. Data collected from medical record review, interviews and clinical examinations were analyzed using chi(2) tests, t itests, and nonparametric tests. Multivariable proportional odds models were developed, using the likelihood ratio test and adjusting for several demographic, behavioral, and biological factors. Thirteen percent of participants had OC only; 12.8% had OHL only; 4.6% had OC-OHL; whereas 69.7% had neither. Occurrence of OC-OHL was independently associated with CD4+ counts less than 200 cells per microliter (adjusted odds ratio [OR] (95% confidence interval {CI}) = 13.4 (6.6, 27.2) and CD4+ counts 200-499 cells per microliter (OR = 3.9 [1.9, 8.1]); current smokers (OR = 2.3 [1.4, 3.8]); and whites (OR = 1.7 [1.1, 2.5]). Combination antiretroviral therapy was protective (OR = 0.5 [0.3, 0.9]). In an HIV-1-infected population, lower CD4+ cell counts and smoking were important independent risk indicators for joint occurrence of OC and OHL.