Pope John Paul II lent his prestige to Nancy Reagan's crusade against drug abuse today, commending her in a 25-minute papal audience for her work against what he called "this grave social evil."

Afterward, when they were joined by Mrs. Reagan's entourage of 15, which included her hairdresser and her personal maid, the pope's eloquence came through in style as well as words. Speaking quietly to her as they exchanged gifts, he took her hand and and held it as he walked her to the door.

"God bless you," the pope told the first lady. "Thank you very much for the visit."

Mrs. Reagan then viewed Michelangelo's frescoes in the Sistine Chapel. Half of the chapel was blocked off for her tour, and surprised tourists waved and applauded when the first lady came into view.

In a letter he gave her, which the Vatican released in a move believed rare for a private audience, the pope called finding "viable solutions to this problem which affects so many of our young people" one of modern society's "great challenges."

Warning of the "enslavement which results from this dependency," the pope's letter said, "The consequences for the family and for society in general are tragic and debilitating."

In particular, the pope called for international cooperation through legislation, law enforcement and therapeutic and rehabilitation programs.

The pope's appeal echoed the sentiments expressed Thursday by the seven heads of government at the economic summit in Bonn for strengthened cooperation in cracking down on international drug use and trafficking.

"Certainly the leaders of society must strive to create the social conditions in which young people are discouraged from seeking refuge in the fantasy world of self-indulgence and drugs," the pope's letter said, "and are inspired and helped to fulfill responsible roles in society."

Warning that "the dignity of the human person is seriously offended by the enslavement which results from this dependency," the pope went on to ask "to what extent this phenomenon is symptomatic of a profound crisis of the social and moral order?"

On her return flight to Bonn, Mrs. Reagan called the meeting a "once in a lifetime experience" and described the pope as "a combination of great strength and gentleness at the same time, which is a rare combination. And he's just a wonderful man."

She said she was taking a message from the pope to President Reagan, but did not disclose the letter's contents.

Security measures were extraordinarily tight throughout Mrs. Reagan's two-day visit to Rome, and today when she arrived at St. Peter's Square the Vatican police blocked off half of it. The first lady's group included John R. Simpson, head of the Secret Service, and agent George Opfer, identified as a "special assistant."

Swiss Guards in orange, blue and red uniforms stood at attention and papal gentlemen in tails welcomed Mrs. Reagan to the Vatican Palace. Upstairs, accompanied by U.S. Ambassador to the Holy See William A. Wilson and his wife, Betty, she was escorted by Archbishop Jacques Martin, prefect of the pontifical household. They passed through papal audience halls and throne rooms to reach the Papal Library where President and Mrs. Reagan were received by the pontiff in 1982.

Inside the library, according to Vatican tradition, the pope sat at his desk and she opposite him. They were alone and spoke in English. "You really can't go into conversations which you have with the pope," she said later. "But it was generally about what I am doing and his equal concern about the problem."

James Rosebush, Mrs. Reagan's chief of staff, said the White House provided the pontiff with a briefing book from the first lady's drug conference last month in Washington that brought together the wives of 17 world leaders.

"A Vatican official told me that the audience was the first time the pope had ever met with the spouse of a head of state on so serious an issue," Rosebush said.

For the meeting, Mrs. Reagan wore a black coat-dress by her favorite designer, Adolfo, and a black hat with an upturned brim edged in white. She carried a black handbag and black gloves, which she almost left behind on the pontiff's desk until a papal aide noticed them.

Afterwards, John Paul greeted each member of the first lady's entourage, including Mrs. Reagan's maid Anita Costelo and her hairdresser Julius Bengtsson.

Mrs. Reagan gave the pontiff a book, "Scribes and Sources" by A.S. Osley, and a crystal box etched with her signature. The pope gave her a silver and mother-of-pearl rosary. She told a Vatican official, as she toured the Sistine and Pauline chapels, that she had brought a book of the pope's sayings, hoping he would sign it for her, but left it at the residence of U.S. Ambassador to Italy Maxwell Rabb, where she has been a house guest.

The first lady arrived at the Vatican in an embassy Cadillac but left in a Ford Grenada. A White House aide said the switch was necessary because the Cadillac would not fit through the entrance to Villa Richardson, residence of the Wilsons, who gave a gala lunch for the first lady before her return to Bonn.

Among the 36 guests were several from the Vatican, including Cardinal Agostino Casaroli, the pope's secretary of state, Cardinal William W. Baum, former archbishop of Washington and highest ranking American in the Vatican, and movie stars, including actress Audrey Hepburn.