In 1931 Castle went to Puerto Rico sponsored by the Rockefeller Foundation International Health Board in a public health project. He conducted a several-month study for the Rockefeller Anemia Commission, as part of the Rockefeller Foundation's work in trying to combat hookworm in the Caribbean. Anemia was widespread on the island because of the endemic parasite hookworm and tropical sprue, the latter a disease which scientists thought possibly related to diet. Castle was assisted by Cornelius P. Rhoads, known as Dusty, who was affiliated with the Rockefeller Institute in New York and later became head of Memorial Hospital for Cancer Care and Research.