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Pope Benedict XVI criticised the 50-year-old US trade embargo on Cuba as he wrapped up a three-day visit to the island, urging reconciliation and greater freedoms.
He said: "May no one feel excluded ... from taking up this exciting search for his or her basic freedoms, or excused from this by indolence or lack of material resources, a situation which is worsened when restrictive economic measures, imposed from outside the country, unfairly burden its people."
The Pope has met Cuban leader Fidel Castro in Havana, Cuba after addressing 600,000 people in Revolution Square.
The Pope did not cite the government by name, but in his address in Havana, he urged Cuban authorities to let the church more freely preach its message and educate its young in the faith in schools and universities.
The remarks came before Benedict's eagerly anticipated meeting with Fidel Castro.
In his remarks to the 600,000-strong crowd, the pope issued his strongest denunciation of religious intolerance yet in Cuba.
He referred to the biblical account of how people persecuted by the Babylonian king "preferred to face death by fire rather than betray their conscience and their faith."
He said people find freedom when they seek the truth that Christianity offers.
The pope demanded greater freedom for the Catholic Church in Cuba during an unusually politicised Mass before hundreds of thousands of people today in the shrine of the island's communist revolution.
He also denounced "fanaticism" that tries to impose its truth on others.
Pope Benedict has met with Cuban revolutionary icon Fidel Castro after saying mass in Havana, the Vatican has said.
The meeting comes towards the close of the pope's three-day visit to the Communist-run island, during which the pontiff has called for greater freedoms, and a bigger role for the Roman Catholic Church in Cuban society.