Karnal bunt disease of wheat is an internationally quarantined disease and is a challenge to the grain industry due to restricted international movement. Previous studies conducted at the Punjab Agricultural University have shown that the resistance to this disease is largely governed by major genes for partial resistance having cumulative effects. As many as nine different major gene loci have been identified in the host and data shows that the gene-for-gene relationship holds good in this host-pathogen system. The fungal pathogen, Tilletia indica, shows high variability due to its heterothallic nature. The pathotypes of the pathogen are not genetically uniform and are populations having genetic variability with in isolates. In this paper, using theoretical models, the effect of  frequency of avirulence/virulence alleles at different pathogenicity loci in the pathogen isolates, corresponding to different resistance/susceptibility loci in the host (considering gene-for-gene relationship), on the expression of the disease in the host for different pathotypes is discussed. The paper highlights the importance of this aspect in designing disease management strategies.