One person is fighting for life and another 19 have been taken to hospitals across Melbourne after crashes involving more than 20 vehicles in regional Victoria.
The Western Freeway was closed in both directions between Bacchus Marsh and Ballan due to the pile-ups just before 4pm at Myrniong, about 58 kilometres west of Melbourne.
That incident, which police have blamed on fog, came amid separate commuter chaos for those heading to Geelong and other parts of western Victoria.
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A truck driver died in a collision with a train in Geelong, halting V/Line services to the city from the capital, and the West Gate Freeway was shut for almost an hour.
Ambulance Victoria said 20 patients were taken to hospital from the Myrniong crash, including one to Royal Melbourne Hospital in a critical condition.
The other 19 were taken in stable conditions to Royal Melbourne, Ballarat Base Hospital, Sunshine Hospital and Footscray Hospital.
There were no suspected injuries involved in the West Gate collision, Victoria Police confirmed.
The West Gate Freeway began reopening by 5pm and traffic eventually cleared but the Western Freeway and V/Line services between Lara and Waurn Ponds were still cut beyond 9pm.
Motorists heading towards Ballarat were being diverted off the freeway at Bacchus Marsh where they needed to take a lengthy detour using Geelong-Bacchus Marsh Road into Geelong, then Geelong-Ballan Road.
Those heading towards Melbourne were diverted off the freeway at Greendale-Myrniong Road to take the Old Western Highway and Pentland Hills Road.
For drivers leaving Melbourne, wider detours should be considered including the Princes Freeway to Geelong then the Midland Highway to Ballarat.
A spokesperson from Vic Roads urged motorists to slow down.
"There are reports of extensive fog covering parts of the Western Freeway," they said.
"Motorists should slow down, drive to the conditions and have their headlights on to be better seen."
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West Gate Freeway closure causes peak hour chaos
Earlier, police closed all outbound lanes of the West Gate Freeway from Grieve Parade, Altona North, after a collision, but reopened two lanes about 5pm.
All drivers bound for Geelong were directed onto a single lane at the Grieve Parade exit, which caused delays of more than 90 minutes, stretching as far back as the Domain tunnel.
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Truck driver killed in collision with train
The traffic chaos happened within hours of a fatal collision between a truck and a train in North Shore, near Geelong, which closed the train line for those travelling between Lara and Waurn Ponds.
About 25 passengers were evacuated from a V/Line train after it slammed into a truck, killing the truck driver on impact.
Major delays on the Geelong and Warrnambool lines continued into the night with emergency services still at the scene.
A spokesperson from V/Line said trains would continue to operate between Southern Cross and Lara, with coaches to transport passengers between Lara and Waurn Ponds.
The same arrangements were in place west of Geelong to Warrnambool.
A spokesperson said the lines would remain closed between Lara, on the Melbourne side of Geelong, and Waurn Ponds, on the Warrnambool side, until further notice.