After World War II, Spedding founded the Institute for Atomic Research and the Ames Laboratory of the Atomic Energy Commission. He directed the Ames Laboratory from its founding in 1947 until 1968. It was initially established on the grounds of Iowa State College. Permanent buildings were constructed that were opened in 1948 and 1950, and subsequently named Wilhelm Hall and Spedding Hall. Spedding was "universally acknowledged as one of the world’s foremost experts on the identification and separation of rare earths". He developed an ion exchange method of separating and purifying rare earth elements using ion exchange resins. He later used ion exchange to separate isotopes of individual elements, including hundreds of grams of almost pure nitrogen-15.