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This has lead to writers coming up with two different but functionally similar solutions to this problem. Either have the microbe get really really big or have the hero get really really small. This runs almost entirely on You Fail Biology Forever and the most extreme form of Square-Cube Law.
In many cases, the wee beasties aren't disease germs, but simply single-celled organisms; favorites are amoebae and paramecia. In other cases, they're normal parts of the human body; antibodies, or blood cells.
- Pokémon has Solosis and its evolutions, all of which are giant cells. There's also Deoxys, a giant, humanoid space-virus.
- Most mushi are pretty much giant magical microbes.
- In the Don Rosa Scrooge McDuck story "The Incredible Shrinking Tightwad", Scrooge and Donald are eventually shrunk down to microscopic size due to the effects of a malfunctioning shrinking ray, and are menaced by a horde of microbes.
- In a Super Goof story, a villain used a ray gun to enlarge animals. In the final battle, Super Goof was pitted against a van-sized amoeba.
Film -- Live-Action
- Evolution used a giant microbe. Technically, it's an amoeba...
- The B-Movie The Flesh Eaters features the titular micro-organisms joining together to become one large creature.
- Star Trek III: The Search For Spock has a set of microbes that get supersized thanks to the Genesis Effect. Later, they get so big that Captain Kruge gets to have a fight with one of them!
- In Fantastic Voyage, the heros had to survive being caught in the crossfire of anti-bodies versus bacteria, "recticular fibers" that clog the intake ports, an direct attack on Grant and Cora by antibodies, and white corpuscles.
- In some Choose Your Own Adventure books that involved some shrink-ray device, a few bad endings had microbes (e.g. paramecium, or white blood cells) attach themselves to a object which returns to normal size. In the case of a amoeba, it took Kentucky for breakfast, then Lousiana for lunch. Even at their normal microscopic size, they look very large.
- The oldest known example of this trope dates back to a french pulp adventure Une Invasion de Macrobes / The Invasion of the Macrobes published in 1909.
- The Belgian sci-fi/horror book La sortie est au fond de l'espace by Sternberg starts like this. All the microbes start growing, making the Earth uninhabitable in a series of scenes between horror and Black Comedy. For the survivors who fled in a spaceship, It Got Worse.
- In an episode of Star Trek: The Original Series, the Enterprise crew fight a space amoeba at least as big as a planet.
- An episode of Star Trek: Voyager has the crew dealing with Giant Basketball-sized flying viruses.
- On the subject of Star Trek, the original series had its own truly humongous, space-borne and of course Enterprise-threatening example in "The Immunity Syndrome".
- Used in Fringe, with a single-celled cold virus grown to the size of a cucumber. Yes, they did call it a "single-celled virus".
- There's a Yu-Gi-Oh Card Game card called Giant Germ that deals damage and acts like an Asteroids Monster.
- Phyrexian Living Weapons in Magic: The Gathering come into play automatically attached to a 0/0 Germ token. The germ can't survive on its own outside of the weapon, but with a few buffs to its toughness and power it's possible to beat things up with a giant Germ.
- These toys are pretty much this trope(in plush form).However not all are infectious microbes. One is yeast, a few are cells.
- The third boss of El Viento is a huge single-celled organism.
- Morpha from The Legend of Zelda: Ocarina of Time, whose Boss Subtitles identify it as a Giant Aquatic Amoeba.
- City of Heroes has Hamidon, giant single-celled organism and endgame raid boss.
- In Xenoblade Chronicles, these show up as enemies in the Bionis' Interior, and all possess the trait of being highly resistant to physical attacks.
- The comic Irritability played with this once, with Chappy bragging about his victory over a giant plankton.
Chappy: It was huge!
Tatanya: Like this? (Pictures a building-sized plankton screeching "RAR!")
Chappy: ...for a plankton. (Pictures himself grasping that same plankton, now about the size of an apple, and saying "I have u now!")
- Johnny Bravo episode "The Incredible Shrinking Johnny" ends with an amoeba accidentally enlarged to giant size, which proceeds to chase Johnny and Carl down the street.
- Superman the Animated Series featured a brief appearance by ameoba enlarged to human size in the episode that introduced the giant ape "Titano".
- The Amoeba Boys are a gang of three dimwitted crooks in The Powerpuff Girls. They're about the size of humans, and sort of float along the ground.
- Swat Kats had a legion of gigantic purple bacteria monsters in its second episode, "The Giant Bacteria". The trouble is, they didn't much look like germs, possessing eyes, mouths and a definite torso shape with arms and legs, due to the first one having originally been an ordinary guy (more or less) who gets mutated by Mad Scientist Dr. Viper.
- The largest known single-celled lifeforms on the planet are amoeba-like protista called xenophyophores. They run about ten centimeters across. Small by monster standards, but positively Kaiju-sized by cell standards. They are found exclusively in the deepest parts of the ocean.