In 1934, Robert W. Wilson designated P. nesodytes as a new species after discovering a mouse bone (a right ramus of the mandible). He writes, “The outstanding character of P. nesodytes is its large size, which is greater than any living species of Peromyscus native to the United States.” The only larger mice known are the extant mice of the genus Megadontomys, which are found in Mexico and Central America.
The engrossed size of P. nesodytes follows Foster's rule of insular gigantism and dwarfism in which some rodents become enlarged because of their inhabitation of islands lacking a multitude of predators. Foster’s rule also helps to explain the diminished sizes of the extinct pygmy mammoth and the critically endangered island fox of the Channel Islands.
The habitat of P. nesodytes was exclusively located on the northern California Channel Islands. Remains of P. nesodytes have been found on San Miguel Island and Santa Rosa Island, California. The northern Channel Islands were once connected as a “super-island” called Santa Rosae, but increased sea levels have separated the islands for thousands of years.
P. nesodytes probably became extinct because of the possibly accidental introduction of a smaller mouse, Peromyscus maniculatus, by the Chumash people who lived in the Santa Barbara area. The Chumash traded on the northern Channel Islands and could have been unknowing transporters of P. maniculatus to the islands. Phillip Walker notes, “Considering the nesting and feeding opportunities provided by the plant foods traded to the islands, it is possible that Peromyscus occasionally crossed the Santa Barbara Channel secreted in baskets of cargo.”
P. maniculatus probably fared better in avoiding the most frequent mouse predator on the islands, the barn owl, than P. nesodytes. A possible example of this is shown in an archaeological site on San Miguel Island, Daisy Cave. Daniel Guthrie writes, "The smaller numbers of P. maniculatus from the lower levels of Daisy Cave may be due to preference by owls for the larger mouse species [P. nesodytes] that was on the island at the time."
- Ainis, Amira F. and Rene L. Vellanoweth (2012). Expanding the Chronology for the Extinct Giant Island Deer Mouse (Peromyscus nesodytes) on San Miguel Island, California, USA. Journal of Island & Coastal Archaeology 7:146–152.
- Guthrie, D.A. (1993). New information on the prehistoric fauna of San Miguel Island: in F.G. Hochberg, ed., Third Channel Islands symposium, Santa Barbara, CA, Santa Barbara Museum of Natural History, p. 405-416.
- Wilson, R. W. (1936). "A New Pleistocene Deer-Mouse from Santa Rosa Island, California". Journal of Mammalogy. 17 (4): 408–410. doi:10.2307/1374408.
- Guthrie, D.A. (1998). Fossil Vertebrates From Pleistocene Terrestrial Deposits on the Northern Channel Islands, Southern California: in Weigand, P.W., ed., Contributions to the geology of the Northern Channel Islands, Southern California: American Association of Petroleum Geologists, Pacific Section. MP 45.
- White, J.A. (1966). A new Peromyscus from the late Pleistocene of Anacapa Island, California, with notes on variation in Peromyscus Nesodytes: Los Angeles County Museum Contributions in Science no. 96, p. 1-8.
- Wenner, A.M. and D.L. Johnson (1980). Land vertebrates on the California Channel Islands: Sweepstakes or Bridges? in D.M. Powers, ed. The California Islands, proceedings of a multi-disciplinary symposium, Santa Barbara, CA, Santa Barbara Museum of Natural History, p 497-530.
- Walker, P. (1980). Archaeological evidence for the recent extinction of three terrestrial mammals on San Miguel Island: in D.M. Powers, ed. The California Islands, proceedings of a multi-disciplinary symposium, Santa Barbara, CA, Santa Barbara Museum of Natural History, p. 703-717.