This paper aims to shed light on Italian contribution to the origins of malaria hypothesis, also known as Haldane hypothesis. The first studies on the association between hemoglobinopathies and malaria, in fact, were done in Italy since the end of the 1920s. These studies tried to explain the correlation between malaria and thalassemia observed by clinicians in various Italian regions. Later, since the beginning of the 1940s, this singular correlation was documented by thorough and wide-ranging epidemiological researches that revealed a strong geographic correspondence between the frequency of the thalassemic features and endemic malaria in Italy. These researches raised clearly the question of maintaining the frequency of a gene that, at the time, doomed homozygotes to death within the first two years of life. In 1948, Silvestroni, Bianco and Montalenti started investigating the causes of the persistence of the thalassemic foci in Italy. In 1949 J.B.S. Haldane finally hypothised for the first time an evolutionary advantage of thalassemic condition due to the concomitant presence of malarial infection. Since 1948, Montalenti and Haldane had various occasions to discuss on this topic. I try to demonstrate the role of Silvestroni, Bianco and Montalenti's research and data on the formation of Haldane hyphothesis.
