The prominence recently given to the Rous sarcoma has increased the confusion of hypotheses about malignancy. With a view to clarification, one may say that there are three simple hypotheses of outstanding importance, viz.: (1) the living virus hypothesis, which regards living viruses as the actual and effective cause of both the avian and the mammalian disease; (2) the autogenous enzyme hypothesis, which ascribes both diseases to the development within living cells of an ens malignitatis resembling an enzyme rather than a virus; and (3) the “chronic irritation” hypothesis, which explains mammalian malignancy on this principle and considers fowl sarcoma to be of a different nature.