In this study, 2 experiments determined the effects of increasing dietary concentrations of deoxynivalenol (DON) on performance, intestinal morphology, and measures of innate immunity in broilers and turkeys. For experiment 1, the 3-wk study used 5 concentrations of DON (up to 18 or 10 mg of DON/kg of feed in broilers or turkeys, respectively) from naturally contaminated corn. The BW gains were cubically or quadratically affected by the increasing dietary concentrations of DON for broilers and turkeys, respectively; however, feed consumption was not affected. For experiment 2, the birds were subsequently injected or not injected with lipopolysaccharide (LPS) 24 h before tissue and blood sample collection. Dietary DON had no effect on intestinal crypt depth, but linearly increased the mid-ileal villus height in broilers (P = 0.04). An interaction was observed between the LPS challenge and the dietary DON with regards to heterophil to lymphocyte ratio (P < 0.05) in broilers, but not in turkeys. The cecal tonsil cell phagocytosis of microbeads was not affected by the dietary concentration of DON either with or without the subsequent LPS challenge for both broilers and turkeys. Conversely, the phagocytic capacity of cecal tonsil cells to engulf killed Staphylococcus aureus was significantly reduced (over 2.5-fold) when broilers were fed the highest concentration of dietary DON (non-LPS-challenged; P < 0.05). However, diets containing DON showed no effects on broilers when they were challenged with LPS. Antibody-dependent phagocytosis (S. aureus) was not affected in turkeys fed DON. Overall, corn naturally contaminated with up to 18 or 10 mg/kg of DON (broiler or turkey, respectively) reduced bird BW gain at 21 d of age, reduced antibody-dependent phagocytosis of previously killed S. aureus by cecal tonsil cells in non-LPS-challenged broilers, and greatly decreased heterophil to lymphocyte ratios in LPS-challenged broilers.