Up to 25,000 postal workers, including drivers in Birmingham and Coventry, have started striking in a row over pay and jobs that is threatening huge disruption to mail deliveries.
Around 80 drivers based at the Mail Centre in Newtown, Birmingham, and a further 100 from the National parcels hub in Coventry were joining a series of 24-hour walkouts from 4am.
The Communication Workers Union said members in areas including the West Country, London, East Anglia, the Midlands and Scotland would take industrial action on Friday, Saturday and Monday - the biggest outbreak of unrest since a national stoppage in 2007, with more disruption threatened in the coming months.
The union's executive has also decided to hold a national ballot of its 160,000 postal members in September which could lead to nationwide strikes in October.
Strikes have hit several areas of the country, notably London and parts of Scotland, in recent weeks in the dispute over pay, jobs and services.
The action is now spreading to other parts of the country, and for the first time will involve drivers of Royal Mail's lorries.
The Royal Mail condemned the strikes and clashed with the union over how many workers will take action, claiming it will only involve 12,000 employees.
Bosses said more than 90% of staff nationally will continue to work normally, and that with the exception of local strikes, the "vast majority" of customers' services will be operating normally over the next few days.
Paul Tolhurst, Royal Mail's operations director, said: "The CWU is again saying one thing and doing another. Publicly they say they want modernisation yet they write regularly to members saying union policy is to oppose change on the ground.
"They agreed with us only last week a timetable for further talks on change, yet they now announce a national strike ballot. Their behaviour beggars belief."
Dave Ward, deputy general secretary of the CWU, said: "Postal workers are sick and tired of an incompetent management running their business into the ground. Workers are busier than ever and being treated badly. The current round of cuts in jobs and services is unacceptable."
Drivers based in Northampton, Birmingham, Coventry, London and Essex will be among workers striking for 24 hours on Friday, while postal staff in Somerset, Bristol and Edinburgh will take action on Saturday. Industrial action will spread to Ipswich and Suffolk on Monday, with further areas set to be hit later next week.