The exchanges of carbon, water and energy between the atmosphere and the Amazon basin have global implications for the current and future climate. Here, the global atmospheric inversion system of the Monitoring of Atmospheric Composition and Climate (MACC) service is used to study the seasonal and interannual variations of biogenic CO2 fluxes in Amazonia during the period 2002-2010. The system assimilated surface measurements of atmospheric CO2 mole fractions made at more than 100 sites over the globe into an atmospheric transport model. The present study adds measurements from four surface stations located in tropical South America, a region poorly covered by CO2 observations. The estimates of net ecosystem exchange (NEE) optimized by the inversion are compared to an independent estimate of NEE upscaled from eddy-covariance flux measurements in Amazonia. They are also qualitatively evaluated against reports on the seasonal and interannual variations of the land sink in South America from the scientific literature. We attempt at assessing the impact on NEE of the strong droughts in 2005 and 2010 (due to severe and longer-than-usual dry seasons) and the extreme rainfall conditions registered in 2009. The spatial variations of the seasonal and interannual variability of optimized NEE are also investigated. While the inversion supports the assumption of strong spatial heterogeneity of these variations, the results reveal critical limitations of the coarse-resolution transport model, the surface observation network in South America during the recent years and the present knowledge of modelling uncertainties in South America that prevent our inversion from capturing the seasonal patterns of fluxes across Amazonia. However, some patterns from the inversion seem consistent with the anomaly of moisture conditions in 2009.