Many of Mubarak's top associates are now being questioned for their activities in the previous regime, but the detention of his sons is by far the most startling development since his Feb. 11 removal from office.
Gamal Mubarak, his younger son, was a top official in the ruling party and was widely seen as being groomed to succeed his father before popular protests brought down the regime.
While the ex-president was in the hospital in the Red Sea resort of Sharm el-Sheikh where he has been living since being removed from power, his sons were taken for questioning to the nearby courthouse by prosecutors from Cairo.
An angry crowd of 2,000 people gathered outside and demanded the two be arrested.
In the early hours of the morning, the head of provincial security in the South Sinai told the crowd that Gamal and his businessman brother Alaa would be detained.
"Brothers, whatever you wanted, you have got ... 15 days," said Maj. Gen. Mohammed el-Khatib, as the crowd erupted in cheers. Egyptian state television later confirmed the order.
As a police van took away the two brothers, the crowd pelted it with water bottles, stones and their flip-flops, a sign of disrespect in the Arab world.
In the two months since Mubarak stepped down, the council of generals ruling the country have initiated a series of investigations of top regime officials.
Associated Press Writers Sarah El Deeb in Cairo and Ashraf Sweilam in Sharm el-Sheikh contributed to this report.