This study sought to establish population-based estimates of the prevalence of co-occurring psychiatric symptoms and either or both drug dependence symptoms or heavy drinking among individuals who test positive for the human immunodeficiency virus (HIV) and to identify the factors associated with such comorbidity. Data from the HIV Cost and Services Utilization Study (HCSUS), a nationally representative sample of HIV-infected adults receiving medical care in the U.S. in 1996 (N = 2,864), were used to estimate the prevalence of comorbidity. Logistic regression was used to identify the independent influences of sociodemographic and HIV-related variables on comorbidity. The authors estimate that 13% of people with HIV receiving care in the U.S. in 1996 had co-occurring psychiatric symptoms and either or both drug dependence symptoms or heavy drinking. The odds of having a comorbid condition were higher for males, heterosexuals, and people with more HIV-related symptoms. The odds were lower for people living with AIDS, African Americans, people who were gay or sexually abstinent, those living with a spouse, those aged 50 years or older, and those with private insurance. Sixty-nine percent of those with a substance-related condition also had psychiatric symptoms; 27% of those with psychiatric symptoms also had a substance-related condition.