Rail firms have advised commuters to take the rest of the week off rather than face travel disruption on the country's busiest line.
Because of major engineering works, the west coast main line between Milton Keynes and Hemel Hempstead will be closed until Sunday.
Silverlink said it would "not be possible to transport all passengers by coach between Milton Keynes and Hemel Hempstead".
It said: "While we are looking into alternative arrangements, many commuters may prefer to arrange their holidays around this period to avoid what will inevitably be a difficult four days for commuting."
There will also be no Virgin trains from Euston to Manchester Piccadilly, but there are direct Virgin services to Manchester from London St Pancras which are unaffected by the work.
The company also recommended that people planning to use the Euston to Manchester route take some time off work.