In the eastern United States, inorganic species account for approximately half of the PM2.5 mass, with sulfate salts comprising the largest fraction. Current strategies for reducing PM2.5 mass concentrations target reducing SO2 to reduce sulfate, but in such a case more ammonium nitrate may form when nitric acid is present. Large-scale chemical transport models suffer from uncertainties associated with emission inventories. To examine how the inorganic PM2.5 concentration responds to changes in emissions, we introduce an observation-based box model, the thermodynamic model with removal (TMR), to estimate responses of PM2.5 to precursor concentrations. TMR assumes that particles are in equilibrium with the gas phase, but the removal rate of total (PM2.5 + gas) nitric acid from the system depends on the gas/aerosol partitioning of this species. The model is used to investigate sulfate, total ammonia, and total nitric acid control strategies for western Pennsylvania during the winter using measurements obtained in the Pittsburgh Air Quality Study. Predictions from TMR are compared with observations and predictions of a chemical equilibrium model (GFEMN), where the perturbation of sulfate or total ammonia does not affect the total nitric acid availability. Results show that TMR predicts more aerosol nitrate to form than GFEMN in scenarios where the total ammonia to sulfate ratio is increased, but model results are similar under ammonia-limited conditions. When sulfate is reduced by 50% during the winter, GFEMN predicts that inorganic PM2.5 mass concentrations will be reduced by 23%, while TMR predicts that there will only be an 8% reduction. For a 50% reduction in ammonia availability, inorganic PM2.5 was reduced by 29%, while for a 50% reduction in total nitric acid a 17% reduction in inorganic PM2.5 was predicted. The analysis suggests the importance of the phase state of the aerosol for the effectiveness of the emission control strategies.