Hundreds of thousands of Venezuelans have taken to the streets to mark 50 days of protests against the unpopular Government of President Nicolas Maduro, with unrest gaining momentum despite a rising death toll and chaotic scenes of night time looting.

At least 46 people have been killed in the worst turmoil faced by Maduro since he won the presidency in 2013.

Venezuelans from civilians to police have been killed, sometimes during increasingly frequent spates of looting or street melees.

Many Venezuelans are furious with Maduro's Government, blaming it for soaring inflation, shortages of everything from food to medicine, and a crackdown on human rights. They are demanding elections, freedom for jailed activists, foreign aid, and autonomy for the opposition-led legislature.

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Major opposition marches took place across the oil-rich nation of 30 million yesterday, with protesters in Caracas brandishing placards that read "No More dictatorship in Venezuela" while in San Cristobal masked youths threw rocks, and a Reuters witness saw two protesters wielding machetes.

Masses of protesters with homemade gas masks and flags shut down a main road in Caracas. Soldiers shut down access to the centre of the city.

"We don't want more deaths. We want salaries that mean something, and medicines. The government invests more in bullets and weapons than in food and education for this country," said Maria Diaz, a 33-year-old lawyer in San Cristobal.

Maduro has been posting videos of himself driving with windows rolled down through various neighbourhoods at night. He drove past a plaza and noted how quiet the streets were. "Look at how peaceful it is here. We're defeating the barricade-builders and violence-bringers," he said.

- Reuters, AP, AAP