A CIA spokeswoman said the agency had no comment on the report in El Pais, which Spanish Interior Minister Jose Antonio Alonso said the government was looking into.
El Pais said CIA aircraft carrying prisoners have made at least 10 stops in the Balearic Islands in the Mediterranean between January 22, 2004 and January 17, 2005.
Separately, a Pentagon spokesman said he was unaware of the report.
"We typically don't talk about the movement of detainees except when they are being transferred or released to another country," said Bryan Whitman. "We don't typically talk about the transit for security reasons."
He said prisoner transfers are "done with a lot of global support out there."
"I don't know all the arrangements, but we clearly have arrangements with countries all across the globe that support the global war on terror," he said.
"I'm not going to get into the specifics of any particular country and our arrangements with them," he added.
The US State Department also refused to comment on the details of the report or on Spain's response to it.
"I'm not aware that we've been officially approached by the government of Spain," State Department spokesman Adam Ereli said.
"Spain is a friend and NATO ally of the United States and our relations will be guided by those principles."