The pope's comments included a greeting to Endeavour commander Mark Kelly, with a wish for his wife U.S. Rep. Gabrielle Giffords to make a speedy recovery. Giffords had surgery to repair her skull Wednesday, four months after being shot in the head at a political event in Tucson, Ariz.
He also offered his condolences to Italian astronaut Paolo Nespoli, whose 78-year-old mother died while he was stationed in space.
But the group had some fun, too. At one point, they floated a coin in front of the cameras to demonstrate zero gravity.
Seated at a table before a television set tuned to NASA's live broadcast from orbit, Benedict said the space fliers are "our representatives spearheading humanity's exploration of new spaces and possibilities for our future." He said he admired their courage, discipline and commitment.
Besides taking phone calls from the pope Saturday, the Endeavour crew was busy inspecting a small gash in the shuttle.
NASA says there's no reason to be worried about the damage, which is about 3 inches wide.
The Associated Press contributed to this report.