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Opis (Akkadian Upî or Upija) was an ancient Babylonian city on the Tigris, not far from modern Baghdad. The precise location of Opis has not been established, but from the Akkadian and Greek texts, it was located on the east bank of the Tigris, near the Diyala River.

Opis is mentioned for the first time at the beginning of second millennium BCE. In the 14th century BCE, it became the capital of an administrative region in Babylonia.

The Babylonians dug the "royal canal" between the Euphrates and the Tigris, which ended near Opis. Nebuchadnezzar built a wall between the two rivers to protect his country from a Median invasion, which also ended near Opis.

In October 539 BCE, Nabonidus defended Opis against the Persian Empire commanded by Cyrus the Great. The Babylonians were defeated and the native population revolted against its government. Without further fighting, Cyrus captured Babylon. Opis was included on the Persian Royal Road, which connected Elam's capital Susa with the Assyrian heartland and—later—the Lydian capital Sardis.

In September 331 BCE, Macedonian Alexander the Great defeated Darius III of Persia at the Battle of Gaugamela, and probably took possession of Opis about the same time as Babylon. A few years later, Alexander was forced by a mutiny at the Hyphasis (now Beas) River to return from the long campaign in India, and European soldiers revolted again at Opis (autumn 324 BCE). Alexander executed the ringleaders of the mutiny, but forgave the rank and file. In an attempt to craft a lasting harmony between his Macedonian and Persian subjects, he married Statira (the daughter of Darius) and held a mass marriage of his senior officers to Persian and other noblewomen at Opis, but few of those marriages seem to have lasted much beyond a year.

Seleucus I Nicator, one of Alexander's Diadochi, founded the Seleucid Empire and built his capital Seleucia on the Tigris on the western bank of the river opposite Opis.

In the second century BCE, the Parthian Empire conquered the Seleucid Empire, including these sister cities. However, the Roman historian Tacitus informs us that in the first century CE, Greek and native inhabitants still had institutions of their own.

In the second century CE, the Parthians moved their regional capital from Seleucia to the eastern bank, and renamed Opis to Ctesiphon.

References