The bike lane will prevent their suppliers from parking delivery trucks outside their shops and restaurants, they say.
'I am a cyclist and I ride my bike many places in the world. But Grand Street is not the place to do that,' said Ernest Lepore, Ferrara's owner.
Ernest Rossi, owner of E. Rossi & Co, a gift shop that's been in the street since 1910, said: 'I would soon be out of business.'
And Victor Papa, a neighbourhood activist, said: 'The mayor is just trying to kill Little Italy and [the adjacent] Chinatown.'
The scene is just the latest sign of a changing balance of power on the city's roads. Suddenly, the cyclists - for so many years at the bottom of the food chain - seem to be on top.
Every year in recent times, cyclists have held a rally outside City Hall, pleading with officials to protect their safety.
A group called Ghost Bikes has placed 45 white bikes on the street since June 2005, each marking a location where a bike rider was killed in an accident.
Now, an environmentally friendly mayor, Mike Bloomberg, is striding towards his ambitious goals of doubling the city's bike lanes by July and doubling the number of riders by 2015.
His administration is establishing new bike lanes at lightning speed. And the protected bike lane, an idea brought back from China by former mayor Ed Koch from his 1979 visit, has become a revitalised tool.
It seems to work well. The number of bike riders has increased 77 per cent since 2002. But while the city's 130,000 cyclists are happier, complaints from car drivers, pedestrians, businesses and residents of the targeted streets have been on the rise.
The tension is apparent beyond Little Italy. In midtown, drivers' tempers were tested when a bike lane and a pedestrian island were opened last month for seven blocks along Broadway from Times Square. That reduced the road from four lanes to two.
In downtown Manhattan, where a narrow path in the City Hall Park was opened to cyclists in July, park users and residents complained that sooner or later someone was going to get hit by a speeding bike.
For Mr Bloomberg, who had to ditch a proposal to charge people to drive in much of the city because of political opposition, the bike lanes make a point about his ability to influence traffic policy and the environment.
When she met the shop owners in Little Italy, Margaret Forgione, Manhattan borough commissioner with the Department of Transport, made it clear that the city was not dropping the plan, though she promised to visit the area once the bike lane was finished to assess its impact on businesses.
But Pak Lew, president of Lendy Electric Equipment & Supply Corporation, may not have the patience to wait.
'The rent in the area is already too high, the parking lots are so scarce. The bike lane would be the last straw,' Mr Lew said.
'I paid US$2 million in sales and payroll tax last year. But I am thinking of moving out of the neighbourhood.'
Tomorrow: London
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