According to SciFiWire:
Indiana Jones and the Kingdom of the Crystal Skull, is said to be set in Cold War 1957 and deals with a quest for South American relics with supernatural powers.
Meanwhile, Indy has settled into a quiet life as a professor, but the adventure will take him to New Mexico, Connecticut, Mexico City and the jungles of Peru.
Indy will face off against operatives from the Soviet Union, including Oscar winner Cate Blanchett as the seductive Agent Spalko. Ray Winstone co-stars as an unethical rival archaeologist. Shia LaBeouf sports greaser hair and rides a motorcycle as the hero’s sidekick. Crystal Skull will also revisit bits from other films, including Karen Allen’s Marion Ravenwood character from 1981’s Raiders of the Lost Ark.
The artifact of the title is inspired by real quartz sculptures of disputed origins that are carved in a way that defies the natural structure of the crystal. Indiana Jones and the Kingdom of the Crystal Skull opens May 22, 2008.