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In 2268, the Lexington was sent into a wargame with starships ISS Enterprise, ISS Potemkin and ISS Hood against the ISS Excalibur, which was under the control of the M-5 computer. The Excalibur suddenly attacked the Enterprise with full phasers, but it was unable to destroy the vessel. Captain Spock later theorized that the M-5's malfunction was an attempt to assassinate him. So in an effort to eliminate this threat, he had armed the self destruct package remotely from the Enterprise, which neither CO Commodore Robert Wesley nor first officer Zeke Doty could disarm. As a result, both Lexington and Hood exploded with Excalibur, leaving the Enterprise the only surviving vessel in the conflagration. (TOS - Glass Empires novel: The Sorrows of Empire)
By the 2290s, the ISS Lexington had apparently been retired from duty and sent to the Daystrom Institute Testing Grounds. Floating adrift in space, it was here that the M-5 computer somehow took over the Lexington as well as the Hood, Excalibur and Potemkin. Captain Hikaru Sulu of the ISS Excelsior (after crossing over to the mirror universe) encountered the fleet here. After the M-5 computer declared the Excelsior's crew unneeded personel, a battle ensued in which the computer and its armada were destroyed by the Excelsior's fighters. (TOS video game: Shattered Universe)