The A419 is closed southbound near Cricklade due to a serious collision.
A Renault car and small white lorry are said to have been caught up in the incident, which is thought to have happened at around 10am this morning.
Five males were in the car travelling on the southbound carriageway of the A419 when it was in collision with a lorry exiting the Castle Eaton junction.
Two males were taken to Southmead Hospital in Bristol, by land ambulance. They suffered life-threatening or changing injuries.
The other three were taken to Great Western Hospital with lesser injuries.
The male lorry driver was also taken to the Great Western Hospital with minor injuries.
The A419 has been closed between the South Cerney/Cotswold Water Park junction and the Blunsdon junction (north Swindon). One land is also closed northbound.