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Comparing industry-standard chamber specs for the two calibers reveals that the 5.56 chamber is slightly larger in diameter than the 223 in the body and neck areas, has slightly longer headspace and, most importantly, a throat configuration both larger in diameter and longer with a more gradual lead angle into the rifling.

Remember that the 5.56×45 chamber originated in select-fire weapons, capable of sustained full-auto fire, which makes guns hot—the larger/longer chamber and more gradual lead of the 5.56 is designed to handle these conditions.

Ammunition for 5.56 and 223 share the same external dimensions, but the 5.56 is loaded to higher pressures. This pressure differential can be exacerbated by firing 5.56 rounds in a smaller chamber, with shorter and steeper throat. As the gun heats up from rapid firing, pressure can increase until a host of bad things happen.

Pierced primers, primers blown into the fire-control system, and stuck cases can all result.

So, to avoid over-pressure—and all the problems that come with it—don’t shoot 5.56 ammo in guns chambered for 223 Rem. 223 Rem ammo can safely be fired in guns chambered for 5.56, but keep the 5.56 out of those chambered for 223 Rem.