Police have advised motorists the M40 will remain closed in both directions between junctions six and four until at least 4.30pm today.
Following a collision between two lorries shortly after 3am, the motorway had to be shut while a clean-up operation took place.
One of the lorry drivers died in the crash.
Police said the road would now reopen at 4.30pm at the earliest, but have warned motorists to avoid travelling on the road, as well as the A40 and the A41 heading into Aylesbury.
Police have also told motorists to avoid the High Wycombe and Stokenchurch areas.
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