ABSTRACT One plant genotype displays a resistance phenotype at one development stage but a susceptible reaction to the same pathogen at another stage, which is referred to here as resistance inversion. In wheat, Fusarium head blight (FHB)-resistant cv. Sumai3 showed a Fusarium seedling blight (FSB)-susceptible reaction whereas FHB-susceptible cv. Annong8455 exhibited FSB resistance when challenged with a Fusarium asiaticum strain that produces deoxynivalenol (DON). The resistance to FHB and FSB in wheat was closely associated with expression of a plant cytochrome P450 gene in response to FHB pathogens and mycotoxins. Quantitative real-time polymerase chain reaction analyses showed that expression of nine defense-related genes in spikes and seedlings was induced by the fungal infection, in which a massive accumulation of a plant cytochrome P450 gene, CYP709C1, was clearly associated with the resistance reaction in both seedling and spike. The FHB-resistant Sumai3 accumulated 7-fold more P450 transcripts than did the FHB-susceptible Annong8455, while 84-fold more P450 transcripts were accumulated in the FSB-resistant Annong8455 than the FSB-susceptible Sumai3. A Fusarium strain with a disrupted Tri5 gene, which is not able to produce the first enzyme essential for trichothecene mycotoxin biosynthesis, also induced more P450 transcripts in FHB- and FSB-resistant cultivars. The fungal activation of the P450 gene was more profound in the FSB-resistant reaction than the FHB-resistant reaction relative to their susceptible counterparts. DON triggered a differential expression of the P450 gene with comparable patterns in spikes and seedlings in a resistance-dependent manner. These results may provide a basis for dissecting mechanisms underlying FHB and FSB resistance reactions in wheat and revealing functions of the cytochrome P450 in plant detoxification and defense.