The (metric designation: 5.6×15mmR) cartridge is a long-established variety of .22 caliber rimfire ammunition, and in terms of units sold is still by far the most common ammunition in the world today.

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The cartridge is often referred to simply as .22 LR and various rifles, pistols, revolvers, submachine guns and even some smoothbore shotguns (No. 1 bore) have been manufactured in this caliber

Performance varies between barrel length and the type of action. For example, bolt-action rifles may perform differently from semiautomatic rifles. The .22 LR is effective to 150 yd (140 m), though practical ranges tend to be less. After 150 yd, the ballistics of the round are such that it will be difficult to compensate for the large “drop”. The relatively short effective range, low report, and light recoil has made it a favorite for use as a target-practice cartridge. The accuracy of the cartridge is good, but not exceptional; various cartridges are capable of the same or better accuracy. A contributing factor in rifles is the transition of even a high-velocity cartridge projectile from supersonic to subsonic within 100 yd (91 m). As the bullet slows, the shock wave caused by supersonic travel overtakes the bullet and can disrupt its flight path, causing minor but measurable inaccuracies.

When zeroed for 100 yd (91 m), the arc-trajectory of the standard high-velocity .22 LR with a 40-gr bullet has a 2.7-inch (69 mm) rise at 50 yd (46 m), and a 10.8-inch (27 cm) drop at 150 yd (140 m).[10] A .22 LR rifle needs to be zeroed for 75 yd (69 m) to avoid overshooting small animals like squirrels at intermediate distances.

As a hunting cartridge, rimfires are mainly used to kill small game up to the size of coyotes. Although with proper shot placement it can kill larger animal such as deer or hog,] it is not recommended because its low power may not guarantee a humane kill. The largest recorded animal killed with a .22 long caliber rifle was a grizzly bear in 1953. Because a .22 LR bullet is less powerful than larger cartridges, its danger to humans is often underestimated. In fact, a .22 LR bullet is capable of inflicting very serious injuries (e.g. the four people wounded, one mortally, during the Reagan assassination attempt) or death e.g. the Kauhajoki school shooting (11 killed and one wounded), the Jokela school shooting (eight killed and one wounded), and the 1979 Cleveland Elementary School shooting (two killed and nine wounded), as well as the assassination of Robert F. Kennedy. Numerous other shooting incidents have demonstrated that .22 LR bullets can easily kill or seriously injure humans. Even after flying 400 yd (370 m), a .22 bullet is still traveling about 500 ft/s (150 m/s). Ricochets are more common in .22 LR projectiles than for more powerful cartridges as the combination of unjacketed lead and moderate velocities allows the projectile to deflect – not penetrate or disintegrate – when hitting hard objects at a glancing angle. A .22 LR can ricochet off the surface of water at a low angle of aim. Severe injury may result to a person or object in the line of fire on the opposite shore, several hundred yards away. Rimfire bullets are generally either plain lead with a wax coating (for standard-velocity loads) or plated with copper or gilding metal (for high-velocity or hyper-velocity loads). The thin copper layer on plated bullet functions as a lubricant reducing friction between the bullet and the barrel, thus reducing barrel wear. Plating also prevents oxidation of the lead bullet. Lead tends to oxidize if stored for long periods. On a plain lead bullet, oxide on the bullet’s surface can increase its diameter enough to either prevent insertion of the cartridge into the chamber, or – with high velocity rounds – cause dangerously high pressures in the barrel, potentially rupturing the cartridge case and injuring the shooter; for that reason, standard and subsonic cartridges usually use a wax lubricant on lead bullets.