The M40 is currently closed southbound at the junction with the A34 at Bicester.
Police said a car and a lorry were involved in an accident at 8.43am.
One driver is believed to be trapped and another is being treated for head injuries.
Paramedics are still on the scene.
The incident follows earlier trouble on the M40 when a broken down vehicle caused tailbacks shortly after 7.30am.
The Highways Agency has advised motorists to expect delays until at least 11am.
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