In this research we estimated the contribution of a major-gene effect to the control of litter size in hybrids between two local populations of the house musk shrew (Suncus murinus). Segregation analysis was performed on the basis of a mixed polygene and major-gene model. The model presumes that two parental populations may differ from each other in gene frequencies and in the values of polygenic effects but not in the major-gene contribution of the trait. Moreover, the peculiarity of the trait – litter size – is taken into account. This trait is not an individual attribute. It characterizes the parental couple and may depend on the genotypes of both parents. Results of segregation analysis of a large hybrid pedigree of Suncus murinus indicate that the parental populations differ in the allele frequency of the major gene (one population is homozygous, while the other contains the two alleles in approximately equal proportions) and in the values of average polygenic effects. Both major-gene and polygenic components are necessary for the correct description of litter size inheritance in interracial hybrids of S. murinus, inasmuch as the exclusion of either of them leads to a significant drop in likelihood. The Elston–Stewart criterion also confirms the Mendelian inheritance of the major gene.