Like all other lemurs, they are native to Madagascar, where they are found in the western dry deciduous forests and further to the north in the Sambirano Valley and Sahamalaza Peninsula.

Giant mouse lemurs sleep in nests during the day and forage alone at night for fruit, tree gum, insects, and small vertebrates.

The first species of giant mouse lemur was described by the French naturalist Alfred Grandidier in 1867 based on seven individuals he had collected near Morondava in southwestern Madagascar.

[5] In 1870, the British zoologist John Edward Gray placed Coquerel's giant mouse lemur into its own genus, Mirza.

This classification was widely ignored and later rejected in the early 1930s by zoologists Ernst Schwarz, Guillaume Grandidier, and others, who felt that its longer fur and bushy tail did not merit a separate genus and instead placed it in Microcebus.

[6] British anatomist William Charles Osman Hill also favored this view in 1953, noting that despite its larger size (comparable to Cheirogaleus), its first upper premolar was proportionally small as in Microcebus.

[7] In 1977, French zoologist Jean-Jacques Petter also favored the Microcebus classification, despite the threefold size difference between Coquerel's giant mouse lemur and the other members of the genus.

[8] The genus Mirza was resurrected in 1982 by American paleoanthropologist Ian Tattersall[5][8][9] to represent an intermediate branch between Microcebus and Cheirogaleus,[5] citing the Coquerel's giant mouse lemur's significantly larger size than the largest Microcebus and locomotor behavior more closely aligned with Cheirogaleus.

[11][12] In 1993, primatologist Colin Groves initially favored the Microcebus classification in the second edition of Mammal Species of the World,[11] but began supporting the resurrection of Mirza in 2001.

[15] The World Wide Fund for Nature (WWF) announced in 2010 that a biodiversity study from 2009 in the gallery forest of Ranobe near Toliara in southwestern Madagascar revealed a population of giant mouse lemurs previously unknown to science, and possibly a new species.

Gray often created mysterious and unexplained taxonomic names—a trend continued with his description of not only Mirza in 1870, but also the genera Phaner (fork-marked lemurs) and Azema (for M. rufus, now a synonym for Microcebus), both of which were described in the same publication.

In 1904, American zoologist Theodore Sherman Palmer attempted to document the etymologies of all mammalian taxa, but could not definitively explain these three genera.

For Mirza, Palmer only noted that it derived from the Persian title mîrzâ ("prince"), a view tentatively supported by Alex Dunkel, Jelle Zijlstra, and Groves in 2012.

[26] Like other cheirogaleids, the dental formula for giant mouse lemurs is 2.1.3.32.1.3.3 × 2 = 36; on each side of the mouth, top and bottom, there are two incisors, one canine, three premolars, and three molars—a total of 36 teeth.

[9] The new population found by WWF in 2010 has an overall lighter color, along with reddish or rusty patches near the hands and feet on the dorsal side of the arms and legs.

Behavioral studies of captive individuals have also been performed at the Duke Lemur Center (DLC) in Durham, North Carolina during the 1990s.

[41][44][45] Both species typically forage between 5 and 10 m (16 and 33 ft) above the forest floor, though Coquerel's giant mouse lemur has been observed on the ground.

[44] They primarily move by quadrupedal running and occasionally leaping between branches, and use the same feeding postures as mouse lemurs, such as clinging to tree trunks.

[25] Slow movements are usually seen in lower, denser foliage when hunting for insects, while more rapid motion and leaping is typically seen at moderate heights of 2–5 m (6.6–16 ft).

[46] Giant mouse lemurs begin foraging moments before the sun disappears,[41] occasionally participate in social activities during the last half of the night,[44][46] and return to one of their nests prior to sunrise.

[41][44][45] During the first half of the night, giant mouse lemurs are more likely to rest for an hour or more, usually at the expense of social activities, but not feeding time.

[41][44][42] Both species sleep in round nests up to 50 cm (20 in) across made of interlaced lianas, branches, leaves, and twigs gathered from nearby trees and woven using the mouth and hands.

[48] Both species usually are solitary foragers,[41][47][49] although the northern giant mouse lemur tends to be the most social, possibly due to its higher population density.

[41][47] Males do groom and call to females when they come into contact, and according to radio-tracking and direct observations at Analabe near Kirindy, they form pair bonds,[41] sometimes briefly traveling together during the dry season.

[40] However, most interactions between adults are infrequent and typically occur later at night and particularly during the dry season in overlapping core areas, often involving chases and other agonistic behavior, and only rarely social grooming.

[52] Giant mouse lemurs use at least eight vocalizations, the most common of which are contact calls, which sound like "hum" or a "hein" and are used when moving and when meeting familiar individuals.

[41] Testicle size in the northern giant mouse lemur does not appear to fluctuate by season,[32] and is so large relative to the animal's body mass that it is the highest among all primates.

[42][32] In contrast, male Coquerel's giant mouse lemurs appear to fight for access to females (contest competition) during their breeding season.

[57] During June and July, at the peak of the dry season, this species relies on sugary excretions from the larvae of hemipteran and cochineal insects as well as tree gums.

Other documented predators of giant mouse lemurs include the fossa (Cryptoprocta ferox), Madagascar owl (Asio madagascariensis), and the narrow-striped mongoose (Mungotictis decemlineata).