Raging forest fires in central Portugal killed at least 57 people, many of them trapped in their cars as flames swept over a road, in what Prime Minister Antonio Costa tonight called "the biggest tragedy of human life that we have known in years."

The deaths occurred in the Pedrogao Grande area, about 150km northeast of Lisbon, where some 600 firefighters have been trying to put out the fires since Saturday, Interior Ministry official Jorge Gomes said.

Gomes said 16 people were killed when their vehicles were engulfed by flames on a road between the towns of Figueiro dos Vinhos and Castanheira de Pera, and three others died from smoke inhalation in Figueiro dos Vinhos.

A huge wall of thick smoke and bright red flames towered over the top of trees near houses in the wooded region.

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"This is a region that has had fires because of its forests, but we cannot remember a tragedy of these proportions," said Valdemar Alves, mayor of Pedrogao Grande.

"I am completely stunned by the number of deaths."

Public broadcaster RTP said there were about 59 injured, including six firefighters.

A man on the balcony of a house in Avelar, Portugal, looks up at a forest fire raging on a hillside above the village. Photo / AP
A man on the balcony of a house in Avelar, Portugal, looks up at a forest fire raging on a hillside above the village. Photo / AP

Fourteen of the injured were in serious condition, RTP said.

Spanish state television showed terrifying images from the neighboring country of several people on a road trying to escape the intense smoke that had reduced visibility to a question of a few meters.

A young man shared a bottle of water with a distraught woman as she stumbled down the road.

Costa said that firefighting crews were having difficulties in approaching the area because the fire was "very intense."

He added that Portuguese authorities were working on identifying the victims and that Spanish rescuers would assist in efforts to control the blazes.

Costa said that while investigations are ongoing to determine the cause of the fire, authorities believe that the high temperatures of 40C in recent days may have played a part.

Portugal, like most southern European countries, is prone to forest fires in the dry summer months.