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After lashing Florida, Isaac - which has killed nine people - is heading towards the northern Gulf Coast.
Louisiana, Florida, Mississippi and Alabama have all declared a state of emergency.
The Republican Party has delayed the start of its Florida convention, which is to formally nominate Mitt Romney as its presidential candidate, by a day.
The National Hurricane Center (NHC) said that at 09:00 GMT on Monday, Isaac was centred about 180 miles (290km) south-west of Fort Myers in Florida, with wind speeds of 65 mph (105km/h), and could reach hurricane force in the following 24 hours.
A hurricane warning is already effect for some 300 miles of the Gulf Coast in four states from Louisiana to Florida.
Hurricane watches have been put in place along the coastlines of western Florida, Alabama, Mississippi and south-eastern Louisiana.
Tropical storm warnings are also in effect for many areas along Florida's Gulf Coast.
Low-lying areas to the north of the Gulf of Mexico are on flood alert.
Some mandatory evacuation orders are in place, says the BBC's Jonny Dymond, in Tampa, Florida.
The Florida Keys have been experiencing rain and strong winds, our correspondent says, but there were few reports of damage.
Isaac is already a large storm and could bring significant damage to areas within 200 miles of its centre.
Fed by the warm waters of the Gulf of Mexico, it is expected to strengthen to a Category 2 hurricane with winds of 105mph (170km/h), and make landfall on Tuesday or Wednesday, somewhere between Florida and Louisiana.
There is also a chance it may hit New Orleans on the seventh anniversary of the devastating Hurricane Katrina.
US offshore oil production is expected to be badly hit, as are the refineries in lowland Louisiana.
BP has shut down oil production in the Gulf and is evacuating its platforms there.
The storm has already caused havoc in the Caribbean, bringing death and considerable damage to Haiti, where at least eight people have been killed; floods and downed power lines affected Cuba.
Three people were missing in the Dominican Republic, officials said, including the mayor of a town near Santo Domingo, who was later confirmed dead.
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