Fire affects virtually all terrestrial ecosystems but occurs more commonly in some than in others. This paper investigates how climate, specifically the moisture regime, influences the flammability of different landscapes in the eastern United States. A previous study of spatial differences in fire regimes across the central Appalachian Mountains suggested that intra-annual precipitation variability influences fire occurrence more strongly than does total annual precipitation. The results presented here support that conclusion. The relationship of fire occurrence to moisture regime is also considered for the entire eastern United States. To do so, mean annual wildfire density and mean annual area burned were calculated for 34 national forests and parks representing the major vegetation and climatic conditions throughout the eastern forests. The relationship between fire activity and two climate variables was analyzed: mean annual moisture balance [precipitation P potential evapotranspiration (PET)] and daily precipitation variability (coefficient of variability for daily precipitation). Fire activity is related to both climate variables but displays a stronger relationship with precipitation variability. The southeastern United States is particularly noteworthy for its high wildfire activity, which is associated with a warm, humid climate and a variable precipitation regime, which promote heavy fuel production and rapid drying of fuels.