The pope appeared in relatively good form, but while his voice was strong he had difficulty at times in uttering his words.
"He's now 83, he's frail, he's not in good health, he has Parkinson's disease, he is full of arthritis in his legs and has trouble walking, but his mind is perfect," said U.S. Ambassador to the Vatican Jim Nicholson.
The audience came a day before celebrations planned to mark his election as pontiff on Oct. 16, 1978. Cardinals and bishops from around the world and official delegations from many countries will attend a Mass in St. Peter's Square at 6 p.m. Thursday, about the same hour then-Polish Cardinal Karol Wojtyla was elected the first non-Italian pope in 455 years.
"It is really remarkable to look back at the 25 years and his impact upon the world and the Church," said Los Angeles Cardinal Roger Mahoney.
Polish pilgrims waved red and white flags and sang Polish songs.
"I thank you from my heart for being here today and during all these 25 years," the pope told his countrymen in Polish. "I am happy I can count on your spiritual support."
Later, in Italian, he invited Romans and pilgrims to join him at Thursday's anniversary Mass "to praise the Lord and thank him for this happy event."
The pope's speaking problems were evident Wednesday as they have been for some months. John Paul gave greetings in various languages, leaving it to aides to read most of his remarks.
However, he held up well, lingering for an hour to greet individual pilgrims and prelates. Among the well-wishers were a group of American cardinals, including Bernard Law, who resigned last December as archbishop of Boston following an outcry over the sex abuse scandal in the archdiocese.
Mahoney said the pope is still very lucid, and, when he greeted Mahoney at the general audience, the pope remembered his visit to Universal Studios in Hollywood in 1987.
Cardinals arriving in Rome for the celebrations have appeared more willing to discuss the pope's health, which has visibly deteriorated in recent months, reports CBS News' Sabina Castelfranco. They say that despite his frailty and speech difficulties, he is still lucid and able to do his work, and insist he has no plans to resign.
However, the cardinals and Vatican officials have grown more willing to talk about what to do if he becomes incapacitated.
Church law has no specific provisions for replacing an incapacitated pope. If he were to become sick, he could delegate some authority but would need to make such a decision himself. There has long been speculation that popes write letters detailing what to do if they became incapacitated, but the Vatican has never confirmed that.
New York Cardinal Edward Egan said Wednesday there was a need to draft provisions to deal with a sick pope, particularly now that modern medicine can prolong life. Egan helped draft the 1983 update of church law which said that specific laws would be created to deal with the situation.
"I do not know why they have not provided us with legislation in this regard," he told reporters. "I would say for any leadership, this is something that's going to have to be addressed, and of course it's not a crisis because it's a great blessing that the medical community has achieved what they have achieved."
Nevertheless, he said: "Yes, I imagine there will be greater insistence now as we're getting older."
English Cardinal Cormac Murphy-O'Connor had an audience with John Paul on Tuesday and said he found him lucid, able to understand everything and respond, yet weak and obviously having trouble speaking.
"I think these next couple of weeks are going to be difficult for him because there are so many functions, but knowing John Paul, he will do it," he said.
The pope's stamina will be tested with Thursday's Mass, Sunday's beatification of Mother Teresa and the lengthy ceremony next week to install 30 new cardinals. Tens of thousands of people are expected to attend the ceremonies. The American delegation is headed by Columba Bush, the president's sister-in-law.
John Paul himself has often suggested he does not intend to resign, saying he will carry out his mission to the end.