Burnet's clonal selection theory extended the idea that each antibody-producing cell makes antibodies of only one specificity, predicting these cells proliferate in response to the detection of antigens, cloning and thus selectively increasing antibody abundance; hence, clonal selection. Burnet also predicted that diversity of antibody specificities needs a cellular mechanism to randomize and create diversity.

Burnet first published his theory in 1957 as "A modification of Jerne's theory of antibody production using the concept of clonal selection," Aust. J. Sci. 20 (1957) 67–69.

In 1960 Burnet shared the Nobel Prize in Physiology or Medicine with Medawar "for discovery of acquired immunological tolerance." See also No. 2578.7.