Due to his casualty studies on mustard gas from an accident during the war in Italy, Rhoads became interested in its potential for cancer treatment. For the rest of his life, his research interest was in developing chemotherapy for cancer treatment, but he served primarily as an administrator and scientific director at Memorial and Sloan-Kettering. From studies of mustard gas, he developed a drug called mechlorethamine or Mustargen. Its success in clinical trials during the war years was the basis for the development of the field of anti-cancer chemotherapy. Rhoads also became interested in total body irradiation, which led to early work on chemotherapy.