Hmr²/Hmr^Df females have significantly reduced fertility compared to controls.

Hmr² suppresses hybrid male lethality of hybrid sons of crosses between D.melanogaster females and D.simulans males. This hybrid rescue is not suppressed if the hybrids also carry Dsim\Hmr^+t8.6 or Dmau\Hmr^+t9.4.

The sterility of hybrid daughters of crosses between D.melanogaster females and D.simulans males is suppressed by Hmr². This Hmr²-dependent rescue of hybrid female sterility is not affected if the hybrids also carry Dsim\Hmr^+t8.6.

Hmr² can rescue to viability the hybrid male progeny of D.melanogaster females crossed to D.simulans males, but these hybrid males remain sterile and have rudimentary testes. Hmr² can rescue the sterility of hybrid female progeny of D.melanogaster females crossed to D.simulans males. The degree of rescue of oogenesis depends on the D.simulans stock used, suggesting that D.simulans stocks are polymorphic for factors that allow rescue of the hybrids. No rescue of fertility is seen in female hybrids derived from Hmr² D.melanogaster females crossed to D.simulans males of the C167.4 strain. However, hybrid females derived from the reciprocal cross (C167.4 D.simulans females mated to Hmr² D.melanogaster males) do show rescue of fertility, suggesting that the genetic bases of fertility rescue in the two directions of crossing are at least partially distinct. Hybrid males derived from a cross of Hmr² D.melanogaster females mated to D.mauritiana males are sterile and have rudimentary testes. Hmr² can rescue the sterility of hybrid female progeny of D.melanogaster females crossed to D.mauritiana males. The degree of rescue of fertility depends on the D.mauritiana stock used. Little or no rescue of fertility is seen in female hybrids derived from Hmr² D.melanogaster females crossed to D.sechellia males (10 D.sechellia stocks have been tested).

Hybrid daughters (from a cross of D.melanogaster females to D.simulans or D.mauritiana males) that carry two D.melanogaster X chromosomes are lethal. This lethality is partially suppressed by one copy of D.melanogaster Hmr².

Crosses between D.simulans strain C167.4 females and D.melanogaster Hmr² males result in hybrids of which females are fertile and males are sterile. The hybrid males have tiny atrophied testes containing no sperm and often have an abnormal abdomen phenotype. All the hybrid females in this cross typically produce eggs, although the degree of rescue of fertility is variable; some females contain only a few, very early stage egg clusters, while in other females oogenesis occurs normally in most cysts. There is a significant decrease in the quality and quantity of eggs and ovarioles containing germline cells as the hybrid females age. Eggs from older females may be ventralised.

Crosses between D.simulans strain Tsimbazaza females and D.melanogaster Hmr² males result in hybrids of which females and males are sterile. The hybrid males have tiny atrophied testes containing no sperm and often have an abnormal abdomen phenotype. A small number of females produce a few eggs (approximately 2 per ovary), although in most cases their ovaries are completely atrophied. The females contain germline cells, but they often have an unusual "doughnut" phenotype, with the germline cells being unusually large with a layer of smaller cells (likely to be follicle cells) surrounding each of the large cells. A large clump of DNA is visible inside the "doughnut" upon nuclear staining and looks like an aggregation of several large nuclei. Eggs may be ventralised.

Crosses between D.simulans C167.4 or Tsimbazaza males and D.melanogaster Hmr² females result in hybrids of which males that survive to adulthood often show a variety of somatic defects (including abnormal abdomens, notched wings, knobby wings and stumpy legs). The frequency of the defects varies with the parental D.simulans strain. Hybrid progeny are sterile, except for hybrid females from crosses involving C167.4 males; 41% of these females show some egg production, although they produce only approximately one egg per ovary and the eggs are small, ventralised or otherwise abnormal. Early stage egg clusters often show the germline cell "doughnut" phenotype.

Hmr² rescues the mitotic chromosome decondensation defect seen in the larval brain neuroblasts of male hybrids produced from a cross between D.melanogaster females and D.mauritiana males.

Rare female hybrids from D.simulans strain C167.4 females and Hmr² males have well developed ovaries that contain large number of mature eggs. The reciprocal cross fails to produce fertile female hybrids, indicating a maternal effect for the female sterility rescue (due to maternal contributions from the nuclear genome). No hybrid male sterility rescue is observed, males have rudimentary testes with no advanced stages of spermatogenesis. Lower levels of hybrid female fertility were also observed in crosses involving D.simulans strains Oxnard and vermilion to Hmr².

Rescues species hybrids that are normally inviable; rescues hybrid females from a cross of D.melanogaster Hmr²/Y males to sibling species females, as well as hybrid males from a cross of Hmr² females to sibling species males.