Two children aged seven were flown to hospital after a crash involving four cars, police and the air ambulance service said.
The crash happened on the A174 near Yearby, outside Redcar, at 10.15am Cleveland Police said.
A police spokeswoman said two children were flown to the James Cook University Hospital, Middlesbrough, while a "number of other casualties" were taken by paramedics to the same hospital.
The crash happened on the A174 near Yearby
The A174 was closed in both directions and was expected to remain shut for a number of hours.
Any witnesses should call the Cleveland and Durham Specialist Operations Unit on 101, quoting reference number 230130.
The Great North Air Ambulance Service said it treated a boy aged seven at the scene before flying him to hospital. The service said he had suffered serious head and leg injuries.
A spokesman said a seven-year-old girl was flown to the same hospital in the police helicopter.
More information about the casualties was expected to be given later.