Naturally mercury-enriched substrate is a long-lived source of mercury to the global atmospheric mercury cycle. Field flux chambers, laboratory gas exchange chambers and micrometeorological methods may be applied to estimate emissions from these sources. However, field chamber experimental design may affect the magnitude of the fluxes measured, and the laboratory chamber only provides a minimum estimate of flux. Many factors, such as mercury concentration and speciation in substrate, light, precipitation, and temperature, influence the emission of mercury from the substrate. Mercury concentration in the substrate is a dominant factor controlling emissions and may be used to predict emissions from regions of mercury enrichment. Mercury fluxes measured from three areas of natural enrichment and three areas with low levels of mercury enrichment are 1-5 orders of magnitude greater than the value applied to global belts of natural enrichment. Preliminary scaling of emissions from one of these areas and for western North America indicates that mercury enriched areas may be significant sources of mercury to the atmosphere, and that their contribution to regional and global atmospheric budgets needs to be reassessed.