The colonization of space goes well, but there are not enough humans to do all the work. So scientists engineered androids which are constructed on one planet. Unfortunately they got infected with a virus and they mutated into monsters. A hero, optically representing a barbarian despite the science-fiction scenario, has to clean this mess up.

The Plague is a traditional shooter of the "run and gun" variety. The player walks through the four side-scrolling levels while shooting everything which moves. There is also bit of platforming and dodging involved: getting hit by enemies result the energy bar to go down which eventually leads to death. The protagonist wields a machine gun which can be upgraded by collecting power ups and makes a big blast when holding the fire button for a time. A limited amount of smart bombs can be used to kill everything on screen. The sprites are relatively big and every level has a boss.

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