A nationwide strike against plans to rewrite the constitution shut down much of Venezuelan's capital before erupting into violence that left at least two young men dead.
President Nicolas Maduro pledged to forge ahead with reshaping Venezuela's government despite the protests and a US threat to levy economic sanctions if he continued.
A coalition of opposition groups called what it described as a "great march" for Saturday, returning to a strategy of direct confrontation with the government after a week of alternative tactics like organising a nationwide protest vote against the constitutional rewrite.
In New York, a diplomat resigned from the Venezuelan delegation to the UN in protest against what he called the Maduro's administration's widespread human rights violations.
UN Ambassador Rafael Ramirez said Minister-Counsellor Isaias Medina had acted dishonestly and been removed from his post.
In Caracas, wealthier, pro-opposition neighbourhoods in the eastern part of the city were shuttered and silent until early afternoon, when improvised blockades left them almost entirely cut them off from the rest of the city.
Groups of masked young men set fire to a handful of blockades and hurled stones at riot police, who fired back tear gas.
The chief prosecutor's office said 23-year-old Andres Uzcategui was killed in a protest in the working-class area of La Isabelica in the central state of Carabobo and 24-year-old Ronney Eloy Tejera Soler died in the Los Teques neighbourhood on Caracas' outskirts.
At least nine people were hurt in protests, the prosecutor's office said.
A public transport strike appeared to have halted nearly all bus traffic and thousands of private businesses defied government demands to stay open during the first major national strike since a 2002 stoppage that failed to topple Mr Maduro's predecessor Hugo Chavez.
Mr Maduro said on national television he will press ahead with plans to rewrite the nation's constitution and that hundreds of Venezuela's largest companies are functioning "at 100%" despite the strike.
In parts of western Caracas traditionally loyal to the ruling party, some stores were closed but bakeries, fruit stands and other shops were open and hundreds of people were in the streets.
The 24-hour strike was meant as an expression of national disapproval of Mr Maduro's plan to convene a constitutional assembly that would reshape the Venezuelan system to consolidate the ruling party's power over the few institutions that remain outside its control.
The opposition is boycotting the July 30 election to select members of the assembly.
"Definitively, we need a change," said teacher Katherina Alvarez. "The main objective is for people to see how dissatisfied people are."
Walking through the streets of Venezuela's capital, opposition leader Henrique Capriles called on people at roadblocks to allow ambulances and other emergency vehicles through.