The origins of strain and sex differences in the number of granule cells in the dentate area of hippocampus were examined in a breeding study employing two inbred strains of mice that differ substantially in granule cell number. Sources of hereditary variation analyzed included autosomes, sex chromosomes, and maternal factors, including cytoplasmic and environmental. The results corroborated those of an earlier study in finding that 80% of the strain variation is attributable to autosomal differences. In addition, there appears to be a cytoplasmic factor that results in a strain-dependent sex dimorphism. The autosomal contribution is attributed to mechanisms operating during the primary phase of granule cell genesis. The possibility that the sex difference results from strain differences in mitochondrial DNA affecting rate of cell death is considered.