Area 42 was the fourth area in Destroy All Humans!. Area 42 was a top secret US Government Base. It had a nuclear test site, an airfield and a Majestic base. In Area 42, Crypto 137 saw his past self, Crypto 136, dead. Crypto then swore revenge upon his "brother's" passing.
There was no fence around the border to the base. Instead, several sign posts stated: "photography is prohibited" and "RESTRICTED AREA". In real life, Area 51 has a similar border set up. The border was marked by orange posts which were hard to see during the day, which caused many to accidentally trespass on the base. The game showed the border patrolled by the Army, while Area 51's borders are protected by a network of ground sensors, security cameras and a private security company. The area around the base was primarily desert and several hills surround the facilities. Area 42 was surrounded by mountain ranges and ridges. One of these ridges, Freedom Ridge, allowed curious tourists to see (and photograph) the entire base without fear of being caught trespassing. The exclusion zone around Area 51 includes Freedom Ridge. Similar hills in the game fell outside the gameplay area, although it was possible that you could have had good views of the base from some of them. The newspaper that reported on events that went on in Area 42 was "The Star Spangled Banner".
The base was operated by General Armquist for Military testing.
Majestic Base: Located at the edge of Area 42 and mainly focused on turning Humans into Mutants and produced radioactive cows. The base was surrounded by Telsa Coils. Crypto destroyed the base with the Saucer.
Military Base: Consisted of Soldiers, Army and Air Force Generals, and sometimes Scientists. The base was surrounded by sentry turrets and most of the base consisted of Barracks and an HQ.
Nuclear Testing Site: A small area that consisted of only 1 building. Only a small amount of Scientists and Soldiers were placed there. There were large holes in the ground due to the nuclear tests and a shooting range was also present.
Airfield: Adjacent to the Military Base. Three hangars were present, and one of them contained the foot of Robo-Prez. There were a few F-86 Fighter Jets, a B-29 Superfortress, and a helicopter, but they were all destroyed when Crypto detonated the nuclear warhead.
- Area 42 was based on Area 51, as well as the running gag of 42 from The Hitchhiker's Guide to the Galaxy.
- After the mission Duck and Cover (the final mission in Area 42), Robo-Prez's foot could be seen in a hangar.
- Soldiers could be seen shooting cows on a road.
- Area 42 was the only area to predominantly feature hostiles instead of Pedestrians.