Thousands of police kept the protesters apart from tens of thousands of visitors attending the Cairo International Book Fair in the suburbs of the Egyptian capital on Friday.
"Enough!" said one banner, in an apparent reference to Mubarak's 24-year rule and his expected decision to run again later this year.
"No to the Renewal [of Mubarak's mandate]," the demonstrators chanted. "No to heredity," they said, referring to speculation that if Mubarak, 76, does not stand his eldest son Gamal will be anointed in his place.
Under the Egyptian system, parliament will elect a single candidate for the presidency in May, whose name will then be put to a referendum in September.
Calls for reform
The opposition has long called for constitutional reform to pave the way for direct elections for the presidency and reduced powers for the incumbent.
About 300 Egyptians protested
against Mubarak last month
Compact squads of police, armed with truncheons and riot shields, patrolled the aisles of the conference hall to keep the demonstrators away from the crowds of book-buyers and publishers.
Visitors were prevented from approaching the venue's mosque from which the demonstration set off while mounted police guarded the perimeter of the showground in the Cairo suburb of Madinat Nasr.
A speaker told the crowd: "During Mubarak's four terms in office, a quarter of a million Egyptians have been jailed. If you want others to follow them, vote for a fifth term."
Demonstrators also chanted slogans against Egypt's relations with Israel and its plans to host a landmark summit in the Red Sea resort of Sharm al-Shaikh on Tuesday between Israeli Prime Minister Ariel Sharon and Palestinian leader Mahmud Abbas.
"Mubarak stands for shame and treason," they shouted. "Down with the treacherous Sharm al-Shaikh summit."
The protesters also called for the release of the several hundred suspects that human rights watchdogs say remain in custody after last October's Sinai bombings, in which 34 people died, many of them Israelis.
The demonstration was organised by the Popular Movement for Change, a coalition of campaign groups that first surfaced two months ago when it organised a protest by about 300 people outside the Palace of Justice.
Under the state of emergency in force since the 1981 assassination of Mubarak's predecessor, Anwar Sadat, demonstrations are normally tolerated in Egypt only on university campuses or outside mosques.