For secondary air pollutants, precursor emissions may impact concentrations in nonlinear and interdependent manners. We explore the nonlinear responses of one such pollutant, ozone, to emissions of its precursors, nitrogen oxides (NOx) and volatile organic compounds. Modeling is conducted for a high ozone episode in the southeastern United States, applying a second-order direct sensitivity method in a regional air quality model. As applied here, the sensitivity method neglects most aerosol and aqueous chemistry processes. Inclusion of second-order sensitivities is shown to enable accurate characterization of response to large perturbations in emissions. An index is introduced to characterize the nonlinearity of ozone response to NO_x emitted from each source region. Nonlinearity is found to increase with the tonnage and emission density of the source region. Interactions among the impacts of emission sources are shown to lead to discrepancies between source contribution attributed to an ensemble of emitters and the sum of the contributions attributed to each component. A method is introduced for applying these “cross-sensitivity” interactions to assess the uncertainty of sensitivity and source apportionment estimates arising from uncertainty in an emissions inventory. For ozone response to NO_x, underestimates in emission rates lead to underprediction of total source contribution but overprediction of per-ton sensitivity.