Police were called to the A303 near Andover at 8.40am, shortly after a collision involving a Vauxhall Astra, a Mercedes food delivery van, a HGV, and a DAF recovery truck.
Three people, all from separate vehicles, were pronounced dead at the scene.
Their families have been informed and are being supported by specialist officers.
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The HGV driver, a 38-year-old man from Donnington, Shropshire, was arrested on suspicion of driving a vehicle while unfit through drugs and causing death by dangerous driving.
He has been released under investigation while enquiries continue, according to a representative from Hampshire Constabulary.
Senior Investigating officer DC Cate Paling said: ‘We are keen to speak with anyone who witnessed the collision, or the moments leading up to it, particularly anyone with dash cam footage.
‘In the immediate moments after the collision, a small white car with a black roof passed the scene and we believe they may be an important witness who we wish to speak with.
‘Anyone who can assist our enquiries should call 101, quoting the reference 44210338980.’