Objective: To determine the degree to which cardiorespiratory insufficiency limits physical performance in adolescents seropositive for human immunodeficiency virus (HIV). Design: Quasiexperimental, case series design. Setting: Rehabilitation physiology laboratory. Participants: Seventeen adolescents (12 women, 5 men; age, 18 +/- 2yr; weight, 74.7 +/- 19.3kg; height, 170 +/- 9cm) with HIV infection (viral load, 22,043 +/- 55,869copies/mL; CD4 count, 499 +/- 210/mL) who were free of comorbid conditions limiting treadmill performance. Main Outcome Measures: Spirometric measurements of oxygen uptake and anaerobic threshold obtained from a peak exercise treadmill test using the modified Bruce protocol. Results: Measured peak oxygen consumption (V) over dot O-2 was 42% +/- 19% lower than expected (p < .025), suggesting a significant functional aerobic impairment (FAI) or peak (V) over dot O-2, less than 73% of expected values. Peak (V) over dot O-2 was only slightly higher (P < .05) than the oxygen uptake requirements for the most intense activities of daily living (ADL). Anaerobic threshold was only slightly higher (p < .05) than minimum ADL intensities. Conclusions: Cardiorespiratory insufficiency and FAI limited the ability to perform even low levels of physical activity in these adolescents with mild HIV seropositivity. Disability identified by quantification of FAI may affect implementation of the American with Disabilities Act and public health policy.