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The long-standing studies into the problem of heterosis on the silkworm and other objects are reviewed. Silkworms are divided by sex for hybridization using the genetic marking of the eggs by sex, an improved method of ameiotic parthenogenesis providing all-female progeny, or the method of obtaining all-male progeny as a result of the death of eggs with female embryos under the influence of two non-allele embryonic lethals balances in the Z-chromosome. The experimental data suggest that heterosis is determined by the heterozygosity of lethals and semilethals, rather than depending on the heterozygosity of all gene types. The number of modifier genes that control viability plays a big role in the vigor of heterosis. An effective method is proposed to enhance the vigor of heterosis through the selection of one or two parents of a hybrid for viability, both of which received a strong semilethal. In hybrids, this semilethal is suppressed by the normal allele, and then a more unbalanced complex of modifier genes initiates a heterosis two to three times more vigorous than in standard hybrids. A method is developed to fix heterosis through the backcrosses of females of the high-heterosis hybrids to the absolutely homozygous males of androgenetic origin obtained from these females. These crosses preserve the main genotype of the hybrid and eliminate lethals and semilethals, and, as a result, heterosis is not damped during standard intrahybrid reproduction.