High-altitude populations using biofuels for household energy may be at health risk due to a combination of altitudinal stress and indoor exposures to biomass smoke. In this article, the authors measure indoor and outdoor breathing level concentrations of PM2.5 and CO during periods of meal preparation in a convenience sample of homes above 3000 m in Cusco, Peru. From July 10 to 21, 2005, 237 measurements were taken during a pilot study at 41 residences. Results show the highest levels of PM2.5 and CO occurred during the early morning in the kitchen when dung and wood were used. Additionally, findings suggest that residential biomass fuel combustion in Cusco results in elevated indoor PM2.5 and CO exposure levels that are of potential human health concern, an issue that may be exacerbated by the physiological impact of living in a high-altitude environment.