According to the National Police of Peru, witnesses reported seeing Neal and Hand leaving Peru for Ecuador by boat in late January.
A State Department official confirmed to ABC News that the couple had not been heard from in almost a month.
"The U.S. Embassy in Lima is aware of the two U.S. citizens who apparently went missing while on a cycling trip in Peru," a State Department official said in a statement to ABC News.
"Consular officers from the U.S. Embassy in Lima are in contact with the families and Peruvian authorities, and are providing all appropriate consular assistance," the statement said. "The Peruvian authorities provided us all assurances that they will do everything possible to locate this couple. Embassy officers will continue to provide all appropriate consular assistance and to follow developments closely."
On Feb. 13, the U.S. Embassy in Peru issued a warning to Americans to beware of a kidnapping threat in the Cusco area from a criminal organization, but the State Department official did not confirm that the couple had been kidnapped, saying only that an investigation was under way. The Cusco area is near Machu Picchu, and is a popular destination for tourists.