To investigate the impact of manipulating stomatal density, a collection of Arabidopsis epidermal patterning factor (EPF) mutants with an approximately 16-fold range of stomatal densities (approx. 20–325% of that of control plants) were grown at three atmospheric carbon dioxide (CO 2 ) concentrations (200, 450 and 1000 ppm), and 30 per cent or 70 per cent soil water content. A strong negative correlation between stomatal size ( S ) and stomatal density ( D ) was observed, suggesting that factors that control D also affect S . Under some but not all conditions, mutant plants exhibited abnormal stomatal density responses to CO 2 concentration, suggesting that the EPF signalling pathway may play a role in the environmental adjustment of D . In response to reduced water availability, maximal stomatal conductance was adjusted through reductions in S , rather than D . Plant size negatively correlated with D . For example, at 450 ppm CO 2 EPF2-overexpressing plants, with reduced D , had larger leaves and increased dry weight in comparison with controls. The growth of these plants was also less adversely affected by reduced water availability than plants with higher D , indicating that plants with low D may be well suited to growth under predicted future atmospheric CO 2 environments and/or water-scarce environments.