The ruling concerned the cooling system at Indian Point Units 2 and 3, which were commissioned in the early 1970s. (Indian Point 1 was shut down in 1974.) Both take in enormous volumes of river water — a combined 2.5 billion gallons a day, or more than twice the average daily water consumption of all of New York City — and use it to create steam for turbines and to cool the reactors. The water is then pumped back into the Hudson, 20 or 30 degrees hotter.

Sucking so much water causes plankton, eggs and larvae to be drawn into the plant’s machinery, or entrained, and the water pressure also causes fish to be trapped, or impinged, against intake screens, the state said.

The plant’s “once-through” cooling system was obsolete by the late 1970s, when the state of the art became “closed-cycle” cooling — more akin to a car’s radiator — which consumes less than 10 percent as much water and kills fewer organisms.

“Conversion from a once-through cooling system to a closed-cycle cooling system, while expensive and involving a potentially lengthy construction process, is nevertheless the only available and technically feasibly technology” for Indian Point to satisfy the “best technology available” requirement of state water-quality regulations, an official of the Department of Environmental Conservation official wrote.

If Entergy fails to overturn the state’s ruling, it could take the fight to Washington. And the New York region’s economic reliance on Indian Point could give the corporation considerable leverage. Even Assemblyman Richard L. Brodsky, a Westchester Democrat who is one of the plant’s loudest critics, said he expected Entergy to “try to get the N.R.C. to back off the requirement” for a water quality certificate.

Other opponents of the plant hailed the ruling.

“The era in which you can take 2.5 billion gallons of water from the Hudson River every day, and return it to the river untreated and polluted — those days are over,” said Mr. Brodsky, who, with the folk singer Pete Seeger, successfully sued to get the state to enforce the clean-water laws at Indian Point. “Entergy has to either stop polluting the river or close the plant. End of discussion.”

Alex Matthiessen, president of the environmental group Riverkeeper, said it was conceivable that Entergy could spend the money to retrofit its cooling system and then reapply to the state. But that would cause a huge delay, he added.

“For all we know, this is it — the beginning of the end,” he said.

Ms. Screnci, the spokeswoman for the Nuclear Regulatory Commission, said the commission was “a ways away from reaching a decision on whether to renew the license.” But she added: “It’s my understanding that the law says that this certification must be in place for us to renew the license. So we’ll be watching to see what occurs in the meantime.”