The A404 is shut because of a serious crash involving a lorry and a pedestrian.
The A404 is closed southbound between Handy Cross and the A4155 at Little Marlow.
Highways England said to expect delays, adding: "The A404 in Buckinghamshire is closed southbound between the M40 (J4) and the A4155 (near Marlow) due to a serious collision involving a lorry and a pedestrian."
Thames Valley Police said: "The A404 has been closed southbound between the Handy Cross roundabout and Marlow due to a serious road traffic collision.
"The road is likely to remain closed for some time and serious traffic disruption is anticipated. Please find alternative routes."
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