The BBC is to cut more than 2,000 jobs in its programme-making divisions.
Mark Thompson says a BBC overhaul will bring £355m savings
The 2,050 job cuts - including 424 announced in December - take total job losses at the BBC to 3,780, saving £355m a year to reinvest in programmes.
They are part of director general Mark Thompson's plans to streamline the BBC. He told staff it was "the toughest period any of us can remember".
The National Union of Journalists said the cuts would "rip the heart out" of the corporation.
Monday's announcement of 2,050 losses comes after news earlier this month that 1,730 jobs would go in support services such as finance and personnel. The 3,780 represents 19% of the workforce.
BBC JOB CUTS BY 2008
TV - 47
Radio & Music - 150
New Media - 58
Nations and Regions - 735
Drama, Entertainment and CBBC - 150
Factual & Learning - 424
News - 420
Sport - 66
Professional Services - 1,730
Total - 3,780
The latest cuts will be made across the production divisions from TV and radio to news and new media.
Mr Thompson said it was "a difficult and painful process but necessary". The cuts and savings will be made over the next three years.
Money saved would go back into programmes, including drama, news and local output, he said.
"This is all money we plan to spend on programmes and content, both to improve the services we deliver to audiences right now and to build strong BBC services in the future," Mr Thompson said.
"All divisions are now finding ways of achieving these savings through genuine improvements rather than crude cuts."
National Union of Journalists general secretary Jeremy Dear said staff were being used as "political pawns" in "an unsavoury and grubby deal between government and senior BBC management".
£52m for Nations & Regions
£47m for TV drama
£45m for News
£32m for New Media
£27m for Radio & Music
£23m for TV factual
£14m for CBBC
"How can hard-working staff maintain quality whilst trying to do not only their own job but that of thousands of their colleagues too?" he said.
"The inevitable result is that staff will face burn-out whilst standards and quality will be damaged."
Union leaders will discuss a response to the cuts later this week but say a ballot for strike action will be called if any redundancies are compulsory.
Luke Crawley, an official at the broadcasting, entertainment and theatre workers' union Bectu, said: "This is the worst day in the BBC's history.
"I can't see how the BBC will deliver all Thompson's promises about new services after ditching so many staff, and life for those who survive is going to be miserable.
"We're not against an efficient, productive BBC, but many of Thompson's proposals are going to make it worse, not better, and that's what we'll be fighting against."
Mr Thompson previously said he wanted to transform the BBC into a "simpler, more agile and creative digital broadcaster".
A three-pronged plan involved a "bold new programme and content strategy" based on excellence and a transformation into a "state-of-the art digital broadcaster".
The third aim was to have an "irreversible shift in the culture of the BBC towards simplicity, opportunity and creativity", he said.