Exposure to ambient (outdoor-generated) fine particulate matter (PM(2.5)) occurs predominantly indoors. The variable efficiency with which ambient PM(2.5) penetrates and persists indoors is a source of exposure error in air pollution epidemiology and could contribute to observed temporal and spatial heterogeneity in health effect estimates. We used a mass balance approach to model F for several scenarios across which heterogeneity in effect estimates has been observed: with geographic location of residence, residential roadway proximity, socioeconomic status, and central air-conditioning use. We found F is higher in close proximity to primary combustion sources (e.g. proximity to traffic) and for lower income homes. F is lower when PM(2.5) is enriched in nitrate and with central air-conditioning use. As a result, exposure error resulting from variability in F will be greatest when these factors have high temporal and/or spatial variability. The circumstances for which F is lower in our calculations correspond to circumstances for which lower effect estimates have been observed in epidemiological studies and higher F values correspond to higher effect estimates. Our results suggest that variability in exposure misclassification resulting from variability in F is a possible contributor to heterogeneity in PM-mediated health effect estimates.