Using a mesoscale atmospheric circulation model, it is shown that relatively modest topography height differences of ∼500 m over 200 km near Zotino (60°N, 89°E) in central Siberia may generate horizontal gradients in CO2 concentration in the order of 30 ppm. In a case study for 15 and 16 July 1996, when Lloyd et al. (2001) conducted a convective boundary layer budget experiment in the area, we show that advection of these gradients disturbs the relation between diurnal concentration changes in the boundary layer and the surface fluxes. This demonstrates that mesoscale atmospheric heterogeneity may have severe impact on the applicability of methods to derive the regional-scale fluxes from CO2 concentrations measurements, such as the convective boundary layer budget method or inverse modeling. It is shown that similar mesoscale gradients are likely to occur at many long-term observation stations and tall towers. We use the modeled concentration fields to quantify the horizontal and vertical variability of carbon dioxide in the atmosphere. In future observation campaigns, mesoscale processes may be best accounted for by measuring horizontal variability over a few hundred kilometers and by attempting to quantify the representation errors as a function of mesoscale conditions.