Manny Ramirez and David Ortiz were among the 104 major league players listed as having tested positive for performance-enhancing drugs in 2003, lawyers with knowledge of the results told The New York Times.
The two were key members of the Boston Red Sox World Series championship teams in 2004 and 2007.
On Thursday in Boston, when Ortiz was asked about the 2003 drug test, he told The Times: "I'm not talking about that anymore," he said. "I have no comment."
Angels center fielder Torii Hunter, a longtime friend of Ortiz's, said he was shocked by the report.
"This hurts, this really hurts," Hunter told ESPN.com's Amy K. Nelson. "I don't know what to think about this. I guess you just never know what people do in the dark.
"I still love him but at the same time it's tough to hear that. I know it's going to be tough on him and tough on his family once this gets out. It's Big Papi, man, it's the Big Dog of Boston and he helped win two World Series with those guys, with the clutch hits. And now all those things are going to be tainted."
Ramirez' agent, Scott Boras, would not comment Thursday, according to The Times.
Ramirez, now with the Los Angeles Dodgers, recently came off a 50-game suspension for violating baseball's drug policy by obtaining a prescription for a banned female fertility drug.
In June, The Times reported Sammy Sosa was on the 2003 list. In February, SI.com reported that Alex Rodriguez was on the list, and subsequently, Rodriguez acknowledged having used banned substances from 2001 to 2003, when he was the Texas Rangers.
Players were tested in 2003 as part of Major League Baseball's survey to determine if it was necessary to impose mandatory random drug testing in 2004. There were no penalties for a positive test in 2003.
As part of the drug agreement between the union and MLB, the results of the testing of 1,198 players also were meant to be anonymous. Penalties began in 2004, and suspensions for a first positive test started in 2005.
Government agents initially obtained search warrants in 2004 for the drug-testing records of 10 players as part of its BALCO investigation that led to Barry Bonds' perjury indictment, but they found the more expansive list on a spreadsheet, obtained additional warrants and seized the larger group of records.
The union went to court, arguing the search was illegal, and three U.S. District judges agreed.
The government appealed, and a panel of the 9th U.S. Circuit Court of Appeals ruled for the government, but the entire 9th Circuit threw out the reversal and decided to hear the case itself. The hearing was in December, and the decision is pending. The losing side could then appeal to the Supreme Court. "Whoever got that list is just playing with Major League Baseball right now," Hunter told ESPN.com. "Either put [the list] away, or just put it out. It was anonymous and now the names are leaking and it's a joke.
"He's still my boy, no matter what. David is a great person and I love him to death. Nothing going to change between us. I'm just shocked just like everybody else, that's all."
Information from ESPN.com's Amy K. Nelson and The Associated Press was used in this report.