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 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.