Leeches are a major threat in Resident Evil Zero. In the early years of Umbrella's viral research, James Marcus - one of the company's founding directors - experimented with the newly-discovered Progenitor virus by combining it with leech DNA. The combination of the Progenitor and the leech genes resulted in the creation of the T-virus, and from there Marcus injected this new viral strain into several live leeches. Other mutated leeches infected with the T-virus were also witnessed during the Raccoon City Destruction Incident.
These leeches were created in 1978 by Professor James Marcus by combining the Progenitor virus with leech DNA to create the T-Virus, and then injecting the T-Virus into their bodies. The virus causes the leech to grow much larger sizes than that of an ordinary leech, and to increase the power of its teeth to the point where it can bite through glass. The most unique characteristic of Marcus' leeches was their ability to learn from their experiences and work together to overcome them, eventually functioning effectively as a single creature. It was at this point that they gained the ability to shape themselves into a roughly humanoid form, seemingly out of a desire to imitate their beloved creator. These creatures, which retain their shape due to a mucous fluid that coats the external leeches in order to provide rigidity, are known as 'Mimicry Marcus'.
Several times in Resident Evil Zero, leech swarms will bond together to form a Mimicry Marcus. They have the basic form of James Marcus, but have more 'floppy' movements than basic zombies due to the lack of bone structure. A Mimicry Marcus is also fairly elastic, being able to stretch and elongate its limbs. It can attack by biting, whipping with its arms, or wrapping its arms around the character and squeezing. When its upper body is destroyed, a Mimicry Marcus' legs will inflate and walk towards the player until it explodes, releasing leeches that will attack the player. Mimicry Marcus is easily damaged by fire, either Molotov Cocktails or Flame Rounds from the Grenade Launcher. If a Mimicry Marcus is burned to death, it will not spawn leeches upon dying.
On July 24, 1998, Marcus used a swarm of Leeches to attack the Ecliptic Express, killing and/or infecting everybody on the train. The train was discovered a short while later by Billy Coen and Rebecca Chambers, by which point many of the passengers had already become zombies.
As shown by diaries found in the Umbrella Research Center, even merely touching a Leech can cause infection. In contrast to normal zombie bites, it takes mere minutes for a human infected by a leech to become a zombie. However, if a queen infects a host, 'she' enters inside the host's body. The host will eventually be able to transform into a 'leech-like' form; however, the time for a queen to fully integrate into Marcus' body took nearly 10 years.
During the outbreak that claimed Raccoon City, the doctors of the Raccoon General Hospital observed that the leeches of the sewer systems had been infected with the T-Virus. These leeches also displayed some hive-mind characteristics similar to the Progenitor leeches' "Mimicry Marcus", but rather than bonding together to create a human form, they would instead swarm a host, drain them of their blood and imbue them with such abilities. This new abomination was somewhat intelligent, crawling through ventilation ducts to surprise its prey. It could be brought down by intense heat, though the leeches would not fall for the same trick twice.
These leeches, like Marcus', served a "queen". This queen reacted differently to the T-Virus and its size increased, making it the size of an adult human. It was eventually killed by a group of survivors on their way out of the Raccoon General Hospital via a sewer exit.