The effects of diet type (corn- vs. wheat-based) and multicarbohydrase addition on growth performance, digesta pH and viscosity, intestinal populations of Clostridium perfringens and lactic acid bacteria, and gut lesion score (from 0 to 4, where 0 = no gross lesions, 4 = severe extensive necrosis) of broiler chickens during oral challenge with C. perfringens (none or 10(8) cfu/bird on d 13) were studied in a 39-d experiment. A total of 1,216 male Ross-308 chickens was assigned to 8 dietary treatments in a randomized complete block design providing 8 replicate pens per treatment. Diets were formulated to meet the NRC protein requirement but were suboptimal in energy level. When compared with birds fed corn-based diets, chickens fed wheat-based diets had inferior (P < 0.01) final BW (2.49 vs. 2.59 kg) and feed conversion ratio (FCR; 1.83 vs. 1.78). Pathogen challenge significantly (P < 0.05) impaired growth performance and increased C. perfringens numbers and average lesion score. Increased (P < 0.01) C. perfringens counts (2.4 vs. 1.5 log(10) cfu/g of digesta) and intestinal lesion score (0.9 vs. 0.4) were observed for challenged birds fed wheat-based diets. No difference in digesta pH and lactic acid bacteria numbers were found among the treatments. Enzyme addition to both the corn- and wheat-based diets increased bird final BW (2.57 vs. 2.51 kg; P < 0.01), decreased overall FCR (1.78 vs. 1.83; P < 0.01), and, in those consuming wheat-based diets, reduced digesta viscosity (from 4.1 to 2.7 mPa.s; P < 0.01). Enzyme supplementation assisted the challenged birds in maintaining their optimal growth performance by improving (P < 0.05) average daily gain (59.5 vs. 56.9 g) in those consuming corn-based diets and FCR (1.83 vs. 1.90) in those consuming wheat-based diets to values similar to those observed in control birds (59.7 g/d and 1.84, respectively). In conclusion, enzyme addition improved growth performance and mitigated the negative effects of C. perfringens challenge.