The CMAQ model in combination with observations for INTEX-NA/ICARTT 2004 are used to evaluate recent advances in isoprene oxidation chemistry and provide constraints on isoprene nitrate yields, isoprene nitrate lifetimes, and NO<sub>x</sub> recycling rates. We incorporate recent advances in isoprene oxidation chemistry into the SAPRC-07 chemical mechanism within the US EPA Community Multiscale Air Quality (CMAQ) model. The results show improved model performance for a range of species compared against aircraft observations from the INTEX-NA/ICARTT 2004 field campaign. We further investigate the key processes in isoprene nitrate chemistry and evaluate the impact of uncertainties in the isoprene nitrate yield, NO<sub>x</sub> (NO<sub>x</sub> = NO + NO<sub>2</sub>) recycling efficiency, dry deposition velocity, and RO<sub>2</sub> + HO<sub>2</sub> reaction rates. We focus our examination in the Southeastern United States, which is impacted by both abundant isoprene emissions and high levels of anthropogenic pollutants. We find that NO<sub>x</sub> concentrations increase by 4–9% as a result of reduced removal by isoprene nitrate chemistry. O<sub>3</sub> increases by 2 ppbv as a result of changes in NO<sub>x</sub>. OH concentrations increase by 30%, which can be primarily attributed to greater HO<sub>x</sub> production. We find that the model can capture observed total alkyl and multifunctional nitrates (∑ANs) and their relationship with O<sub>3</sub>, by assuming either an isoprene nitrate yield of 6% and daytime lifetime of 6 h or a yield of 12% and lifetime of 4 h. Uncertainties in the isoprene nitrates can impact ozone production by 10% and OH concentrations by 6%. The uncertainties in NO<sub>x</sub> recycling efficiency appear to have larger effects than uncertainties in isoprene nitrate yield and dry deposition velocity. Further progress depends on improved understanding of isoprene oxidation pathways, the rate of NO<sub>x</sub> recycling from isoprene nitrates, and the fate of the secondary, tertiary, and further oxidation products of isoprene.