The present study demonstrates the incidence of high lethality of F1 (Dh/+) male mice, the offspring of DDD females and inbred DH (Dh/+) males. Among the newborn pups, the numbers of F1 (Dh/+) males are comparable to those of mice having other genotypes (+/+ male, Dh/+ female and +/+ female), but many F1 (Dh/+) males died before weaning. On the other hand, among the F1 mice from the cross between DH (Dh/+) females and DDD males, there are no biased numbers of Dh genotype pups. These results suggest the existence of defects in the interaction between the male derived Dh gene and the genetic traits of the DDD female.