The infected cow, the fourth ever discovered in the U.S., was found as part of an Agriculture Department surveillance program that tests about 40,000 cows a year for the fatal brain disease.
No meat from the cow was bound for the food supply, said John Clifford, the department's chief veterinary officer.
"There is really no cause for alarm here with regard to this animal," Clifford told reporters at a hastily convened news conference.
Mad cow disease, or bovine spongiform encephalopathy (BSE), is fatal to cows and can cause a fatal human brain disease in people who eat tainted beef. The World Health Organization has said that tests show that humans cannot be infected by drinking milk from BSE-infected animals.
In the wake of a massive outbreak in Britain that peaked in 1993, the U.S. intensified precautions to keep BSE out of U.S. cattle and the food supply. In other countries, the infection's spread was blamed on farmers adding recycled meat and bone meal from infected cows into cattle feed, so a key U.S. step has been to ban feed containing such material.
Clifford said the California cow is what scientists call an atypical case of BSE, meaning that it didn't get the disease from eating infected cattle feed, which is important.
That means it's "just a random mutation that can happen every once in a great while in an animal," said Bruce Akey, director of the New York State Veterinary Diagnostic Laboratory at Cornell University. "Random mutations go on in nature all the time."
The atypical form of BSE that is caused by protein mutation also occurs in humans. Called classic Creutzfeldt-Jakob disease, it is found at a rate of one case per 1 million people worldwide, according to the Centers for Disease Control and Prevention.
"It's not unreasonable to think that something similar could occur in cattle," said Terry Lehenbauer, director of the School of Veterinary Medicine Research Centers at the University of California, Davis. "We just don't know all the science about how this disease develops and is transmitted."
Questions remain about whether the incident will prompt the USDA to change how it tests for the disease. But Mike Doyle, director of the University of Georgia's Center for Food Safety, said the testing system worked because it caught what is a really rare event.
"It's good news because they caught it," Doyle said.
Clifford did not say when the disease was discovered or exactly where the cow was raised. He said the cow was at a rendering plant in central California when the case was discovered through regular USDA sample testing.
Rendering plants process animal parts for products not going into the human food chain, such as animal food, soap, chemicals or other household products.
Dennis Luckey, executive vice president of Baker Commodities, told The Associated Press that the disease was discovered at its Hanford, Calif., transfer station when the company selected the cow for random sampling.
Luckey said the cow died at a dairy and was randomly tagged for the surveillance program.
Michael Marsh, chief executive of Western United Dairymen, said it was an adult cow over 30 months old, not a downed or sick animal, and it appeared normal when it was last observed. He said the cow was first tested April 18.
The disease is not transmitted through casual contact like a virus, but Marsh said government investigators are testing other members of the dead cow's feeding herd, as well as cows born at the same time as the dead cow.
It wasn't known how the cow died, and the name of the dairy where the cow died has not been released. Officials also haven't said where it was born.
"It's appropriate to be cautious, it's appropriate to pay attention and it's appropriate to ask questions, but now let's watch and see what the researchers find out in the next couple of days," said James Culler, director of the UC Davis Dairy food Safety Laboratory.
Culler, an authority on BSE, said the California cow's form of the disease so rarely occurs that consumers should not be alarmed.
"Are you worried about all of the meteors that passed the earth last night while you were sleeping? Of course not," Culler said. "Would you pay 90 percent of your salaries to set up all of the observatories on earth to watch for them? Of course not. It's the same thing."
There have been three confirmed cases of BSE in cows in the United States -- in a Canadian-born cow in 2003 in Washington state, in 2005 in Texas and in 2006 in Alabama.
Both the 2005 and 2006 cases were also atypical varieties of the disease, USDA officials said.
The Agriculture Department is sharing its lab results with international animal health officials in Canada and England who will review the test results, Clifford said. Federal and California officials will further investigate the case. He said he did not expect the latest discovery to affect beef exports.
The National Cattlemen's Beef Association said in a statement that "U.S. regulatory controls are effective, and that U.S fresh beef and beef products from cattle of all ages are safe and can be safely traded due to our interlocking safeguards."
Clifford said the finding shows that safeguards the U.S. government and other nations have put into place in recent years are working. In 2011 there were only 29 worldwide cases of BSE, a dramatic decline since the peak of 37,311 cases in 1992. He credited the decline to effect of feed bans as a primary means of controlling the disease.
Past scares about mad cow disease have affected beef exports to Japan and other countries. Japan banned all U.S. beef imports in 2003 after the first case of mad cow disease was discovered in the United States. Japan resumed buying American beef in 2006 after the bilateral trade agreement setting new safety standards.
The Canadian Food Inspection Agency said Tuesday that the latest finding would not affect trade between the US and Canada.