Genetic disorders are usually considered to be caused by harmful gene mutations, as well as by chromosomal aberrations, including small insertions, duplications and/or deletions. However, as infertile individuals often arise among the offspring of crosses between two fertile mouse strains, we postulate that a certain combination of 'normal' genes with neither gene mutations nor chromosomal aberrations can cause such serious phenotypic alterations as reproductive dysfunction. In this study, we show evidence that a combination of multiple normal genes from two different normal mouse strains manifests a wide range of male reproductive dysfunctions, from benign changes to complete infertility. These abnormal phenotypes are thought to have occurred by epistatic interactions of alleles.