Plavsic, the first woman publicly indicted by the tribunal and the second key figure from the former Bosnian Serb leadership to come to The Hague, voluntarily surrendered to the court on Wednesday.
"I have received the indictment yesterday. I have understood it fully and I plead not guilty to all counts on that indictment," said the 70-year-old biology professor in her first appearance before the court.
During the 1992-95 Bosnian war Plavsic was deputy to Bosnian Serb leader Radovan Karadzic. She took over from him when he was forced from office in 1996.
The indictment says Plavsic, together with other members of the Serbian Democratic Party, served on the war presidency of the Bosnian Serb republic and from July 1991 to December 1992 planned or ordered the ethnic cleansing of tens of thousands of Bosnian Muslims and Croats.
The indictment details a huge catalogue of events in which non-Serbs were executed, tortured and detained in inhuman conditions as the brutal purge gathered pace.
"Having knowledge of such crimes, Biljana Plavsic instead condoned and publicly congratulated the forces that had taken part," the indictment says.
Plavsic's attorney, Krstan Simic, says se was "confused, if not shocked, by what she has been accused of" and wants to clear her name.
Prosecutors plan to try Plavsic later this year, alongside wartime Bosnian Serb parliament speaker Momcilo Krajisnik, arrested last April and to date the leading figure held by the tribunal.
Plavsic's surrender is a major coup for prosecutors as they close the net on more powerful figures up the Bosnian Serb chain of command.
Karadzic and his Bosnian Serb military commander Ratko Mladic are the tribunal's top Bosnian Serb indictees. Chief Prosecutor Carla Del Ponte has urged them to follow Plavsic's example.
Another high-profile indicted individual who has yet to surrender is Slobodan Milosevic, who was ousted as president of Yugoslavia last October. The new government has no plans to turn him over to the Hague.
After the pleas, Plavsic's lawyer tried to convince the judges that his client should not be held at the tribunal's detention unit. The unit currently houses 35 inmates and Plavsic is the only woman.
"Should an area be appropriately adjusted for Mrs Plavsic, she would still be living in a male environment and would be in absolute isolation. We all know what that would mean for the accused. Solitary detention is punishment and this is not something that has been considered in this case," said Simic.
Judge Richard May told Simic that was a matter upon which the tribunal's president, not the trial chamber, should rule.
Chief prosecutor Del Ponte said her office were aware of the problem and would seek a solution.
The tribunal does not grant bail, but can grant provisional release in special cases as it has done for four accused so far.
Croat lawyer Goran Mikulicic says he expects Plavsic to ask tribunal president Claude Jorda to be allowed to return to Bosnia.
"The main purpose of the detention centre is to ensure the accused are present at the trial. She will surely be present because she appeared here voluntarily," he said.
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