We examined the prevalence of HIV, general medical, and psychiatric comorbidities by age based on a recent multisite cohort of HIV infected veterans receiving care: the Veterans with HIV/AIDS 3 Site Study (VACS 3). VACS 3 includes 881 adult patients with HIV infection enrolled between June 1999 and July 2000. Providers reported their patients' CDC-defined HIV comorbidities, general medical comorbidities (based on Duke and Charlson comorbidity scales), and psychiatric comorbidity. Mean age of participants was 49 years and 54% were African-American. The most common HIV comorbidities were oral candidiasis (21%), peripheral neuropathy (16%), and herpes zoster (16%). The most common general medical comorbidities included chemical hepatitis (53%), hypertension (24%), and hyperlipidemia (17%). The mean number of HIV and general medical comorbidities experienced by patients were respectively 1.1 and 1.4 (P < .001). Older (> or = 50 years) HIV-infected patients experienced a greater number of general medical comorbidities than those < 50 years (respectively 1.7 versus 1.2, P < .001). There was no significant difference in mean HIV comorbidity number by age. Based on patient report, 46% had significant depressive symptoms (> or = 10 on 10-item CES-D) and 21% reported at-risk drinking (> or = 8 on AUDIT). Providers reported 32% of patients had anxiety, 4% mania, 4% schizophrenia, and 11% cognitive impairment/dementia. General medical and psychiatric comorbidities constituted a higher disease burden for HIV-infected veterans than HIV comorbidities. Whether these comorbidities are due to antiretroviral drug toxicity or are age or lifestyle-associated conditions, the substantial prevalence of these "non-HIV" comorbidities suggest an important role for general medical and psychiatric management of HIV-infected patients.