Infertility in humans and subfertility in domestic animals are two major reproductive problems. Among human couples, ~15% are diagnosed as infertile, and males are considered responsible in about 50% of the cases. To examine male fertility, various sperm tests including analyses of sperm morphology, sperm count and sperm mobility are usually performed. Teratozoospermia, a condition characterized by the presence of morphologically abnormal sperm, is considered as a symptom of infertility. B10.MOL-TEN1 (TEN1) mice (Mus musculus) show inherited teratozoospermia at high frequencies (~50%). In this study, the polygenic control of teratozoospermia in the TEN1 strain was analysed. A quantitative trait loci analysis indicated three statistically significant loci, Sperm-head morphology 3 (Shm3; logarithm of the odds (LOD) score, 29.25), Shm4 (LOD score, 6.80), and Shm5 (LOD score, 3.58). These three QTL peaks were mapped to 24.3 centimorgans (cM) on chromosome 1, 32.0 cM on chromosome X, and 63.8 cM on chromosome 6, respectively. Another locus that is yet to be determined was also predicted. Shm3 was found to be the major locus responsible for teratozoospermia, and a sequential cascade of interactions of the other three loci was apparent. These results are expected to help understand the mechanisms underlying reproductive problems in humans or domestic animals.