Saudi Arabia's Crown Prince Sultan bin Abdulaziz al-Saud died at dawn on Saturday abroad, the country's royal court said in a statement carried by state media.
Sultan, who was thought to be aged about 86, had been in the United States for medical treatment since June.
As well as heir to the throne of the world's top oil exporter, Sultan had been defense minister and minister of aviation for about four decades.
"With deep sorrow and sadness the Custodian of the Two Holy Mosques King Abdullah bin Abdulaziz mourns the death of his brother and his Crown Prince Sultan... who died at dawn this morning Saturday outside the kingdom following an illness," said the statement carried on state news agency SPA and state television.
Saudi television broke its schedules early on Saturday to broadcast Koranic verses accompanied by footage of the Kaaba in Mecca, Islam's holiest site.
Funeral services will be held in the Saudi capital Riyadh on Tuesday, SPA said.
Widely thought to be next in line after Sultan is Interior Minister Prince Nayef, who was named second-deputy prime minister in 2009.
King Abdullah is in his late 80s and underwent back surgery earlier this month but has been pictured since then in apparently good health.
The king was absent for three months late in 2010 while he underwent treatment for a herniated disc that caused blood to accumulate around his spine.
Prince Nayef, who is in his late 70s, has a reputation as being more conservative than either the crown prince or king.
Unlike in European monarchies, the line of succession does not move directly from father to eldest son, but has moved down a line of brothers born to the kingdom's founder Ibn Saud, who died in 1953.
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