"We have strong belief there are international athletes involved as well," USADA Chief Executive Officer Terry Madden said in a teleconference from his offices in Colorado Springs, Colorado.
Madden would not name the athletes whose "A" samples had tested positive for the steroid tetrahydrogestrinone (THG) nor the number of athletes involved.
But he said: "I know of no other drug bust that is larger than this, involving the number of athletes we have involved... certainly in the anabolic steroid area."
The positive samples were found in the retesting of 350 doping tests at June's U.S. championships and 100 later out-of-competition tests, Madden said.
Several positive samples for the stimulant modafinil also were found in the testing, Madden said.
World 100 and 200 metres champion Kelli White of the United States tested positive for the same stimulant at August's world championships and may lose her gold medals as a result.
Madden would not say whether any of the athletes who tested positive for the steroid THG competed in the world championships.
But he noted that all of the athletes with positive tests for the steroid would be subject to a two-year ban and would be ineligible for next year's Olympics if their 'B' samples are also positive.
The International Association of Athletics Federations (IAAF), as well as the athletes involved, have been notified of USADA's findings, Madden said.
No names are likely to be released until December as the positive tests wind their way through U.S. anti-doping procedures, Madden said.
"What we have uncovered appears to be intentional doping of the worst sort," Madden said in a statement.
"This is a far cry from athletes accidentally testing positive as a result of taking contaminated nutritional supplements. Rather, this is a conspiracy involving chemists, coaches and certain athletes using what they developed to be "undetectable" designer steroids to defraud their fellow competitors and the American and world public who pay to attend sports events."
Madden said USADA first learned of THG when a male, who identified himself as a high-profile coach, called the agency in early June, alleging that certain U.S. and international athletes were using an "undetectable" steroid.
SYRINGE RECEIVED
The person subsequently sent USADA a syringe containing a substance that the IOC-accredited laboratory in Los Angeles later identified as a designer steroid, which would have not been detectable in normal laboratory testing.
The Los Angeles laboratory then developed a test for the steroid and in recent days several positive "A" samples results have been reported to USADA.
Madden described a "designer steroid" as one that is tweaked by chemists to make it undetectable under normal testing.
"This is a very sophisticated designer steroid created by very sophisticated chemists," he said.
"The athletes who did take part in this were very sure of themselves in being undetectable because the substance, although the effects would last months, we believe the detection of the steroid in the body would only last a short period of time, just several days ... three to seven days."
The athletes are now entitled to a testing of the 'B' sample and a review by a U.S. anti-doping panel. Thirty days later, under U.S. Olympic Committee rules, the names of the athletes can be released, Madden said.
