During the Raccoon City Destruction Incident, Umbrella's underground laboratory, NEST, was put under lock down due to William Birkin's rampage and the subsequent t-Virus outbreak he'd unintentionally caused. As the lock down suspended all activities within the facility, Umbrella researchers found Plant 43's behavior to be growing increasingly hostile due to the lack of proper maintenance. As the lock down prevented the team's proper maintenance of the creature, as well as being unable to produce P-ε gas to contain it, Plant 43 inevitably lashed out, killing many of the team before spreading into the ventilation shafts and adjoining rooms.
As it attacked the researchers, Plant 43 had also implanted them with its seedlings. These mutated seedlings would then take root in the victim's bodies as a sort of parasite, and upon gestation, come to wildly alter their host's internal anatomy. This resulted in walking corpses infested with carnivorous mutative vegetation that partially mimicked other human beings to trick its prey, and was able to animate the corpse to noticeable effect, including maneuvering the nervous system for the corpse to walk and use its arms, and manipulating the host's vocal chords to communicate in echoed "clicks". For sustenance, the parasite formed a "mouth" through altering the head of the host to be come a large disguised set of mandibles, with which flesh from victims were transferred into the host's stomach through the throat where the plant's roots converged. These creatures also had large, orange bulbs covering their form that were susceptible to conventional firearms, however, only flames were capable of permanently killing them. They were shown to be unaffected by the release of the P-ε Herbicide into Plant 43's environment, although it had successfully killed the larger plant, ultimately stunting development of any more Ivy Zombies.
These creatures would all be destroyed following the NEST facility's self destruct sequence being activated.
Ivies are only encountered in NEST (or in The Ghost Survivors minigame), and are extremely dangerous due to their extremely quick movements. If grabbed by an Ivy, the player must use a defensive item to escape, otherwise the Ivy will instantly kill the player by crushing their skull in their giant mouth and biting the player's face off. The Ivy have yellowish orange bulbs that can be shot to stop them cold in their tracks and stagger them for sometime allowing a quick escape. Destroying all the bulbs (3-5 per Ivy) will result in the Ivy being knocked out, but the bulbs will regrow over time and the Ivy will get back up and resume its assault minutes later. An Ivy can be permanently destroyed if ignited with flame rounds or the flamethrower. When permanently destroyed, the death animation confirming the kill sees the Ivy's entire body becoming fully consumed, with a large plume of smoke and vapor signifying it turning into a charred corpse. In emergencies, an Ivy can be killed without shooting its bulbs with high powered weapons, like Leon's magnum or Claire's high power handgun ammo, but they will get up again and require quite a lot to put down with this method.