Acute and chronic exposure to wildfire smoke can cause numerous documented cardiopulmonary effects, although determining the casual components within the thousands of different chemicals found in both the particle and gas phases remains a toxicological challenge. Specifically, little work has been done to evaluate and predict toxicity of wildfire smoke including 1) how toxic is wildfire smoke compared to other pollutants, 2) which components in wildfire smoke are responsible for adverse health outcomes, and 3) whether the toxicity of wildfire smoke is governed by fuel type and combustion conditions. In this research project, we evaluated lung toxicity, cardiac toxicity and mutagenicity of particulate matter (PM) from flaming and smoldering phases of five biomass fuels (oak, peat, pine needles, pine, and eucalyptus). Biomass smoke condensates were collected from a quartz-tube furnace generation system coupled to a multistage cryotrap. The samples were chemically analyzed and assessed for lung toxicity by oropharyngeal aspiration in mice (non-inhalation exposure study) and mutagenicity in Salmonella. Biomass smoke PM was also directly delivered to mice or rats for inhalation exposure testing for lung and cardiac toxicity tests. Results from the aspiration exposure study showed that, on an equal mass exposure basis, the eucalyptus (flaming) and peat (flaming) smoke PM induced significant lung toxicity potencies (toxicity per mass of PM) compared to smoldering smoke PM, while high levels of mutagenicity potencies were observed for the pine (flaming) and peat (flaming) smoke compared to smoldering smoke. When effects were adjusted for emission factor (which reflects exposure based on mass of fuel consumed), pine (smoldering) and pine needles (smoldering) smoke PM had the highest mutagenicity emission factors (toxicity per thermal energy of fuel combustion) and these were approximately 5, 10, and 30 times greater than those reported for open burning of agricultural plastics, wood burning cookstoves and municipal waste combustors, respectively. The inhalation exposure study also demonstrated that the peat (flaming and smoldering) and eucalyptus (smoldering) smoke elicited significant inflammation in mouse lungs. No responses were seen in aspiration and inhalation studies for emissions from oak smoke. Peat (smoldering) smoke also sensitized rats to post-high fat meal cardiometabolic responses, including significantly increased cardiac isovolumic relaxation time and proinflammatory blood monocytes. Overall, the lung toxicity potencies agreed well between aspiration and inhalation studies with the results showing that although flaming smoke contains much less PM mass than smoldering smoke, it was, on a mass basis, more toxic and mutagenic than smoldering smoke, and that fuel type is also a controlling factor. Knowledge of the differential toxicity of biomass emissions will contribute to more accurate hazard assessment of biomass smoke exposures.