John Paul II will jet into Denver, Colorado, for the start of a four-day visit to the United States where he will be confronted by many followers who are fundamentally at odds with the Vatican over some of the most emotive issues at the fore of contemporary public debate.
He will also have his first meeting with Bill Clinton, who has made a point of championing abortion rights and gay liberation - but still managed to attract 44 per cent of the Catholic vote, some of whom will now be praying that the US President can liberalise papal opinion.
Vatican aides have said the two men will concentrate on discussing world issues, like Bosnia, Somalia and the Middle East, but - given their differences - conversation seems likely to stray on to the 'moral agenda' and Mr Clinton's domestic policy. The 45-minute exchange - billed by some as 'the Old Pope versus the Young President' - is unlikely to be very comfortable.
Officially, the Pope is in the US to attend World Youth Day, an annual Roman Catholic bonanza, which is expected to attract 500,000 people to Denver, temporarily doubling the city's population, filling hotels for miles around and sending short- term home rentals rocketing up to dollars 20,000 ( pounds 13,600). They are not all well-wishers. A platoon of pro-choice activists have already set up camp outside a local Planned Parenthood clinic, surrounded by barbed wire and under the eye of a squad of police in riot gear.
The Pope arrives, hotfoot from a visit to Jamaica and Mexico, to find himself confronted by the depressing evidence of polls highlighting the gulf between the Vatican and many of the US's 59 million Roman Catholics, some of whom appear to be happy to cast aside the Church's teachings while remaining loyal to its name.
The visit is the pontiff's third trip to the continental US and, in a country that has the highest rate of divorce and pregnancy in the industrialised West, it has already generated a bout of national soul-searching about moral standards, and modern Catholicism.
A USA Today/CNN Gallup poll found that, while the majority of Catholics liked the Pope, most (73 per cent) would sooner follow their own consciences rather than papal doctrine. An overwhelming majority - 84 per cent - said they rejected the ban on artificial birth control, and 76 per cent supported allowing priests to marry.
One of the few areas that will provide comfort to the pontiff as he rifles through these statistics is abortion: the same poll said that 58 per cent wanted it banned altogether, while a Newsweek survey found that most people felt the Church's position is 'about right'. It remains one of the most divisive issues in the US.
Millions of Catholics were enraged by Mr Clinton's nominee for surgeon general, Joycelyn Elders, who last year accused religious anti-abortionists of having 'a love affair with the foetus'. In the same remarks, Dr Elders derided abortion opponents for being led by a 'celibate, male-dominated Church', touching on another issue where the Pope will find no shortage of Vatican critics.
Polls also indicate that more than half of the US's Catholics favour the ordination of women, a policy the Vatican has so far firmly resisted. In the past few days pro-ordination protesters have been gathering in Denver in the hope of impressing their views on the papacy.
The apparent disparity between what the Church says and what it does is just as hotly disputed. In recent years the US Catholic Church has been rocked by a succession of sex scandals in which priests have been exposed as persistent child abusers. Since 1982, allegations of child abuse have been made against 400 priests - and some estimates suggest that as many as 2,500 priests have molested youngsters over the past decade.
Many Catholics have been less than impressed by the Church's reluctance to push for the prosecution of errant clergy - further evidence that there may be many half-hearted waves in the throng that welcomes the Popemobile.