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The demonstrators, who represented 112 non-governmental organisations, shouted "Turkey is secular, will remain secular" and "Independent Turkey" and protested against Erdogan's Justice and Development Party (AKP), which has roots in political Islam.
Overwhelmingly Muslim, Turkey is governed by secular laws that separate religion and state.
Since winning 2002 elections, Erdogan's government has alarmed secularists by promoting an increase of religious schools, seeking to lift a ban on wearing Islamic headscarves in universities and government offices and filling senior government posts with Islamists.
Erdogan, a devout Muslim, denies trying to lead the country down a more Islamist path.
In a speech to the demonstrators Sener Eruygur, head of the staunchly secular Kemalist Thought Society (ADD) and a former army general, suggested that Erdogan had ambitions to become Turkey's next president.
"There are plans to invade the sublime presidential office," Eruygur said. "We will not allow that."
Parliament, where the AKP has a comfortable majority, will next May elect a successor to President Ahmet Necdet Sezer, a secularist.
In a July interview with Reuters Erdogan said religious belief should not bar anyone from becoming head of state and did not rule out seeking the presidency.
The president's veto power and control of top appointments give him considerable political clout.
The demonstrators ended the march at Anitkabir, mausoleum of Mustafa Kemal Ataturk who founded the secularist Republic of Turkey in 1923.
Among the protesters were retired army generals and officers.
Turkey's military, which drove a government from power as recently as 1996, views itself as the ultimate guardian of the country's secular order. But it has seen its powers trimmed in recent years by reforms designed to allow the country to join the European Union. Reuters