The nature of genetic variation in litter size and its components was examined using results of long term selection and of crossing selected lines of mice. Selection for small and for large litters produced strains with mean litter size of approximately 6 and 15, respectively. The large litter size line showed a period of renewed response after 45 generations of selection, following a period of 15 generations with no response. The relative contribution of genotype of the dam and of the embryo to prenatal survival was examined using results of selection, crossing and embryo transfer. Genotype of female carrying the litter was responsible for most of the observed differences. Genes for poor survival expressed by the embryo were present in some strains, but accounted for less variation than did maternal genotype. Information from the selected lines and from crosses among them provided evidence for dominance of genes affecting fertility and prenatal survival and additivity of genes affecting ovulation rate and body weight. The information was used to suggest a model for more effective exploitation of heterosis using breeds or strains of animals of known performance for different components. The extent of genetic variation for prenatal survival suggests that natural selection in this species may not always be for maximum survival. It is suggested that the ability to reduce litter size after conception, in response to nutritional or other stress, may at times be of selective advantage, contributing to maintenance of genetic variation in survival rate.