Previously isolated susceptible host mutants were used in a genetic and functional study of the resistance response of barley specified by resistance gene Mla₁₂ to the fungal pathogen Erysiphe graminis f sp hordei. Mutant M66 represents a defective allele of Mla₁₂, whereas M22, M82, and M100 represent mutations in loci unlinked to Mla₁₂. Intermutant crosses of the latter three show that susceptibility in M82 and M100 is caused by allelic, recessive mutations that define the Nar-1 gene (necessary for Mla₁₂ resistance gene 1), whereas the semidominant mutation in M22 defines a second unlinked locus, Nar-2. We show that both genes are required for resistance specified by Mla₁₂ in different genetic backgrounds of barley. Nar-1 maps on barley chromosome 2 within an ∼6-centimorgan restriction fragment length polymorphism interval: this is 0.5 centimorgans from the anthocyanin pigmentation gene Ant2. Quantitative cytological analysis showed that functional alleles of Mla₁₂, Nar-1, and Nar-2 are required for triggering a cell death reaction of attacked host cells at early stages during infection. Functional alleles of all three genes were also required for high-level transcript accumulation of barley defense-related genes that encode chitinase, peroxidase, and pathogenesis-related protein-1. The data support the hypothesis that host cell death and high-level accumulation of defense-related gene transcripts, which are under common control of Mla₁₂, Nar-1, and Nar-2, are crucial events of race-specific resistance to powdery mildew.