Former Bosnian Serb Interior Minister Mico Stanisic has surrendered to the UN tribunal at The Hague and has been taken into custody.
Mico Stanisic was an aide to fugitive leader Karadzic
Mr Stanisic, 50, has been indicted for 10 crimes against humanity and war crimes allegedly committed during the 1992-1995 Bosnian war.
The indictment says he was responsible for the persecution of Bosnia's Muslims and other non-Serbs in 1992.
Mr Stanisic was a close adviser to the fugitive ex-leader Radovan Karadzic.
The alleged crimes listed on the indictment include "persecutions, extermination, murder, torture, inhumane acts (including forcible transfer) and deportation".
In an interview with the Bosnian Serb SRNA news agency, Mr Stanisic said he was innocent of the charges.
"I do not feel guilty," he said. "I am ready for The Hague, because truth and justice are my defence."
Mr Stanisic flew out of Belgrade airport for The Hague on Friday.
Since January this year, four Serb generals have surrendered to the tribunal to face charges.
The BBC's Matt Prodger in Belgrade says the Serbian government has brokered the surrenders in quick succession, anxious to show that it is making progress towards fulfilling its obligations to the tribunal before the European Union issues a feasibility study in a few weeks time.
Both Serbia and Croatia have been under renewed pressure since Kosovo's former Prime Minister Ramush Haradinaj won international praise for his immediate surrender when he was indicted on Tuesday.
Our correspondent says Serbia's record is poor. More than a dozen indictees are still thought to be on Serbian soil.
Croatia has also been criticised by the chief UN war crimes prosecutor, Carla del Ponte, for failing to arrest a former general, Ante Gotovina. If he fails to turn up in the coming days, talks on Croatia's entry into the EU may be postponed.