Karadzic's family was always unwavering in its support for the soft-spoken former psychiatrist, wanted for orchestrating the Srebrenica massacre 10 years ago this month.
Karadzic is wanted to stand trial at the Hague war crimes tribunal, and Nato has stepped up the pressure over the last two months, raiding the family's homes in Karadzic's wartime stronghold of Pale and arresting the couple's son Aleksandar in early July for 10 days.
"Our family is under constant pressure from all sides. Our life and our existence is jeopardised," Ljiljana Zelen-Karadzic told APTN in a short, emotional interview shown on Bosnian and Serbian television stations on Thursday.
"Between loyalty to you and to the children and grandchildren, I had to choose and I have chosen. It is very painful for me to ask you and yet I do. I beg you with all my heart and soul to surrender. It will be a sacrifice for us, for the sake of your family."
"It is very painful for me to ask you and yet I do. I beg you with all my heart and soul to surrender"
wife of Radovan Karadzic
Karadzic and his military chief Ratko Mladic were indicted in 1995 by the UN war crimes tribunal in the Hague over the Srebrenica massacre of 8000 Muslims and the wartime siege of Sarajevo in which 10,000 people were killed.
After two years of relative freedom, Karadzic went underground in 1997. He is rumoured to be protected by hardline Serb nationalists in Serbia, Bosnia and Montenegro.
"In hope that you are alive and that you can make decisions by yourself, I'm begging you to make this decision," Zelen-Karadzic said. "From my own state of helplessness I'm now doing the only thing I can: I'm begging you.".
About 200,000 people died in the 1992-95 Bosnian war, mostly Bosnian Muslims. Nine Serbs and Bosnian Serbs are still on the run from the Hague tribunal for their role in the conflict.
Mladic, along with Karadzic, was
indicted in 1995
The international community has also cracked down on Karadzic's support network, through visa bans, asset freezes and the sacking of Bosnian Serb officials, to no effect.
British General David Leakey, the commander of the European Union peacekeeping force in Bosnia, told Bosnian television Zelen-Karadzic's plea showed Karadzic needed to surrender.
"He is a disgrace for his country and he has abandoned his country and he should turn himself in," Leakey said.
But Karadzic's brother Luka told Beta news agency he disagreed. "The call is a result of the outrageous pressure the family was subjected to. What if Radovan is, for a long time, unable to see this message, what if he is not in a position to make any decision by himself?" he said.
Both Karadzic and Mladic have resisted numerous pleas from Serb and Bosnian politicians to surrender. The West is adamant that neither Bosnia nor Serbia will get into Nato or the European Union until the two faced trial.