Aerobic capacity and physical functioning decline with age and chronic illness. The extent of physical disability is unknown in older HIV-infected adults, who represent a rapidly growing proportion of HIV/AIDS patients in the United States. We performed functional performance testing including treadmill testing in 32 HIV-infected male veterans aged 40-69 years. Controls were 47 healthy male subjects tested previously in the same exercise laboratory. HIV-infected subjects were classified as younger (40-49 years, n = 12) or older age (50+ years, n = 20). Peak aerobic capacity (VO2peak) was significantly reduced in the older vs. younger HIV subjects [19.1 mL/kg/min +/- 5.7 (mean, SD) vs. 25.2 +/- 4.2, p = 0.01]. VO2peak was reduced 41% +/- 15% (mean, SD) in HIV-infected subjects compared to expected values from age-matched healthy controls. Regression analyses show a similar decline in VO2peak with age in HIV-infected and healthy controls. Mean 6-min walk distance was not significantly different between the HIV-infected age groups, and was reduced only 8% compared to expected values for healthy adults. Current CD4 count and HAART exposure were similar in the two age groups and were not significantly associated with VO2peak. Anemia (HCT <35%) was significantly associated with reduced VO2peak (p = 0.02), but this association was not independent of the effect of age (p = 0.1). We conclude that older HIV-infected adults have markedly impaired aerobic capacity but maintain the capacity to undertake day-to-day activities. Additional physiologic and metabolic testing is needed to measure the effect of HAART toxicity and primary aging on aerobic capacity, and to determine if older HIV-infected adults are at greater risk.