In C 3 plants, CO 2 concentrations drop considerably along mesophyll diffusion pathways from substomatal cavities to chloroplasts where CO 2 assimilation occurs. Global carbon cycle models have not explicitly represented this internal drawdown and therefore overestimate CO 2 available for carboxylation and underestimate photosynthetic responsiveness to atmospheric CO 2 . An explicit consideration of mesophyll diffusion increases the modeled cumulative CO 2 fertilization effect (CFE) for global gross primary production (GPP) from 915 to 1,057 PgC for the period of 1901-2010. This increase represents a 16% correction, which is large enough to explain the persistent overestimation of growth rates of historical atmospheric CO 2 by Earth system models. Without this correction, the CFE for global GPP is underestimated by 0.05 PgC/y/ppm. This finding implies that the contemporary terrestrial biosphere is more CO 2 limited than previously thought. mesophyll conductance | CO 2 fertilization | carbon cycle | gross primary production | photosynthetic model T o reach Rubisco, the carboxylating enzyme of the Calvin cycle, CO 2 molecules must diffuse through two consecutive segments of a continuous pathway in leaves of C 3 plant species. The first segment connects leaf intercellular air space with ambient air and is controlled by stomata; the second one consists of mesophyll layers from intercellular air space to stroma of chloroplasts where Rubisco resides (1, 2). These two stages differ in the media through which CO 2 moves. Diffusion in the first segment (stomatal diffusion) is through gases only; that in the second segment (mesophyll diffusion) occurs in a variety of media including liquids and lipids, i.e., cell walls, plasmalemma, cytosol, chloroplast envelope membranes, and stroma. The path length of this mesophyll diffusion is generally shorter than that of stomatal diffusion (2). However, diffusion of CO 2 through liquids is several orders of magnitude slower than it is through gases; diffusion through lipids in membranes is even slower than it is through liquid water (3), although it may be facilitated by aquaporin-like channels (4). Consequently, mesophyll layers constitute a major barrier for CO 2 movement inside leaves (5-9).However, the importance of this mesophyll diffusion limitation for photosynthesis has yet to be reflected in carbon cycle modeling. Current large-scale carbon cycle models (10, 11) have explicitly considered stomatal diffusion but not mesophyll diffusion. Most carbon cycle models use some form of the biochemical model of Farquhar, von Caemmerer, and Berry (FvCB) for modeling photosynthesis (12). In theory, the FvCB model should use the CO 2 concentration at the site of carboxylation inside the chloroplast (C c ). Nevertheless, most modelers have knowingly or unknowingly applied it directly to the CO 2 concentration inside the substomatal cavity (C i ). Since C c can be much smaller than C i , because of the mesophyll resistance to CO 2 diffusion, a compensating adjustment is needed to correct...