Pauling gained an interest in immunology after giving a lecture on the magnetic properties of hemoglobin in Michigan in May 1936. Karl Landsteiner of the Rockefeller Institute attended the lecture and afterwards approached Pauling and requested that they meet and talk. Landsteiner, also familiar with hemoglobin, worked with it in his discipline of immunology. When he approached Pauling, Landsteiner was one month shy of sixty-eight years old, and he was an established scientist in his field. In 1901, he had determined that different blood types exist in human beings, and he had received the Nobel Prize in Medicine for this work in 1930.

At first, Pauling doubted his ability to contribute valuable information to Landsteiner's investigations of antibodies, which are proteins that fight infection, yet in the end they both gained from the interaction. In particular, Landsteiner wanted to understand why each foreign protein, or antigen, introduced into a living organism has its own specific antibody. Immediately following their talk Pauling read Landsteiner's recently published book, The Specificity of Serological Reactions. When Pauling went to Cornell University in late 1937 he and Landsteiner spent several days discussing immunology. Pauling was flattered that Landsteiner took an interest in him and devoted so much time educating him on immunology. Landsteiner gained a newfound passion for his research and was bounding with ideas after talking with Pauling.

Landsteiner and Pauling developed a strong professional and personal friendship that lasted until Landsteiner's death in 1943.