The creation of new atmospheric particles from in situ nucleation influences climate through cloud-aerosol interactions and may negatively impact human health. Although recent observations show that nucleation is widespread in the eastern United States, the corresponding pathways remain uncertain. Combining extensive field measurements in Pittsburgh, Pennsylvania, with an aerosol dynamics and chemistry model assuming ternary NH3-H2SO4-H2O nuclei formation, we show excellent model-measurement agreement and predictive capability. The ternary NH3-H2SO4-H2O nucleation model is successful in predicting the presence or lack of nucleation on 19 out of 19 days with complete data sets in July 2001 and on 25 out of 29 days in January 2002. Reductions of ammonia emissions are predicted to decrease the frequency of nucleation events during both summer and winter, with a more dramatic effect during the summer. The response to changes in emissions of sulfur dioxide during the summer is counterintuitive. Reductions of sulfur dioxide and the resulting sulfate by up to 40% actually increase the frequency of the summer nucleation events. Modeling predicts the opposite effect in winter, with reductions of sulfur dioxide leading to fewer nucleation events.