After Alexander's death of malarial fever in 323 B.C., the Macedonian commander in Egypt, Ptolemy, who was the son of Lagos, one of Alexander's seven bodyguards, managed to secure for himself the satrapy (provincial governorship) of Egypt. In 306 B.C., Antigonus, citing the principle that the empire Alexander created should remain unified, took the royal title. In reaction, his rivals for power, Ptolemy of Egypt, Cassander of Macedonia, and Seleucus of Syria, countered by declaring themselves kings of their respective dominions. Thus came into existence the three great monarchies that were to dominate the Hellenistic world until, one by one, they were absorbed into the Roman Empire.

The dynasty Ptolemy founded in Egypt was known as the line of Ptolemaic pharaohs and endured until the suicide of Cleopatra in 30 B.C., at which time direct Roman control was instituted. The early Ptolemies were hardheaded administrators and business people, anxious to make the state that they created stable, wealthy, and influential. The Ptolemies had their eyes directed outward to the eastern Mediterranean world in which they sought to play a part. Egypt was their basis of power, their granary, and the source of their wealth.

Under the early Ptolemies, the culture was exclusively Greek. Greek was the language of the court, the army, and the administration. The Ptolemies founded the university, the museum, and the library at Alexandria and built the lighthouse at Pharos. A canal to the Red Sea was opened, and Greek sailors explored new trade routes.

Whereas many Egyptians adopted Greek speech, dress, and much of Greek culture, the Greeks also borrowed much from the Egyptians, particularly in religion. In this way, a mixed culture was formed along with a hybrid art that combined Egyptian themes with elements of Hellenistic culture. Examples of this are the grandiose temples built by the Ptolemies at Edfu (present-day Idfu) and Dendera (present-day Dandarah).

The last of the Ptolemies was Cleopatra, the wife of Julius Caesar and later Mark Antony. During her reign, Egypt again became a factor in Mediterranean politics. Cleopatra was a woman of genius and a worthy opponent of Rome. Her main preoccupations were to preserve the independence of Egypt, to extend its territory if possible, and to secure the throne for her children. After the ruinous defeat at Actium in 31 B.C., Cleopatra was unable to continue the fight against Rome. Rather than witness the incorporation of Egypt into the Roman Empire, she chose to die by the bite of the asp. The asp was considered the minister of the sun god whose bite conferred not only immortality but also divinity.

Data as of December 1990