Hench started his career at Mayo Clinic in 1923, working in the Department of Rheumatic Diseases. In 1926, he became the head of the department. While at Mayo Clinic, Hench focused his work on arthritic diseases, where his observations led him to hypothesize that steroids alleviated pain associated with the disease. During this same time, biochemist Edward Calvin Kendall has isolated several steroids from the adrenal gland cortex. After several years of work, the duo decided to try one of these steroids (dubbed Compound E at the time, later to become known as cortisone) on patients afflicted by rheumatoid arthritis. Testing of the hypothesis was delayed because the synthesis of Compound E was costly and time-consuming, and Hench served in the military during World War II. The tests were conducted successfully in 1948 and 1949.