Three children and a woman from the same family have died in a collision between a people carrier and a heavy goods vehicle.
The crash between the family's silver Subaru people carrier and a white HGV took place near a railway overbridge on the A40 to the west of Oxford on Monday night.
The victims have been named in reports as Zoe Powell, 29, from Chinnor in Oxfordshire, her two daughters Amelia, four, and Phoebe, eight, and her six-year-old son Simeon.
Two other passengers in the Subaru, reported to be her 30-year-old husband Joshua and their 18-month-old daughter, were taken to the John Radcliffe Hospital in Oxford, where they both remain in a critical condition.
Police said the driver of the HGV, a 56-year-old man, suffered minor injuries.
The force said they were called at 9.50pm, adding they received "multiple" calls from the public.
Senior Investigating Officer Sergeant Dominic Mahon, of the serious collision investigation unit, based at Bicester, said officers were in the very early stages of the investigation into what he described as an "incredibly tragic" and "horrendous" incident.
Appealing for help from the public, he said: "I would appeal to anybody who was driving in the area at the time of the collision and witnessed what happened to please contact 101, or make a report online, quoting reference number 43200321914.
"I would also urge anybody who has dash-cam footage of the incident or either of the vehicles just prior to the incident to please not share this publicly, but contact police with this detail."
Sgt Mahon warned against speculating about the cause of the collision, adding: "We will leave no stone unturned to ascertain what has caused this tragedy.
"The next of kin of the family have been made aware and are being supported by specially trained family liaison officers.
"The thoughts of all of us at Thames Valley Police, along with our partners who have assisted at the scene or at the hospital, are with the families at this incredibly difficult time.
"I would like to also pay tribute to our officers, first responders and medical professionals, who dealt with this collision.
"Our officers and colleagues from the other emergency services were dealing with an extremely upsetting scene, and I would like to thank them for the work that they carried out overnight."