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Global change-induced alterations in litter quality and soil moisture regime will likely impact grassland C and N dynamics, but how these changes interact with edaphic properties across the landscape is unclear. We measured the effects of litter quality, soil type, soil moisture level, and soil drying-rewetting frequency (D-RW) on microbial C and N mineralization of litter and soil organic matter (SUM) in a full-factorial, controlled incubation experiment. Four levels of litter quality (no litter; or litter from Bouteloua curtipendula grown under 280, 380, 500 mu L L-1 CO2) were surface-applied to three contrasting soils common to Blackland Prairie landscapes: an upland Mollisol,. a lowland Vertisol, and a fluvial Alfisol. Different soil moisture regimes were tested by incubating soils at four moisture levels (air-dry, 25%, 35%, or 50% water-holding capacity, WHC) and by drying-rewetting soils 0, 1, 2, 4 or 8 times over the 112-d incubation period. Litter additions stimulated microbial activity, increasing total CO2 production (i.e. C mineralized from litter + SUM decomposition) up to 17x more than no-litter controls (average 3 x) and decreasing net N mineralization up to -3 x less (average -0.5 x) due to greater microbial N immobilization. Neither C nor N mineralization, however, was affected by litter quality. For all soils, litter decomposition increased with increasing WHC and D-RW frequency, but the average percent of total CO2 derived from litter was a negative function of SUM content. Similarly, net N mineralization also was positively correlated with soil WHC and affected most strongly by soil type (Alfisol < Mollisol < Vertisol). Net N mineralization responses to D-RW events was also soil-specific, with Alfisol soils showing no response and Mollisol and Vertisol soils decreasing after 4 D-RW events. Our results suggest that predicted changes in rainfall patterns and its interactions with soil type across the landscape will control short-term C and N mineralization responses in grasslands to a greater extent than atmospheric CO2-induced changes in litter C:N ratio for this common species of prairie grass. Published by Elsevier Ltd.