Incubation of polioviruses with human intestinal fluid is known to result in molecular and antigenic modification of the virion surface. Studies with different inhibitors of serine proteases suggested that trypsin in the intestinal fluid is most likely responsible for the primary cleavage of VP 1. However, minor differences could be distinguished between the final cleavage products produced by purified trypsin and intestinal fluid, respectively. Other enzymes present in intestinal fluid may thus contribute to the modification of polioviruses in vivo. No evidence was obtained in favour of any biological significance of these further modifications. Another serine protease plasmin, which is generated in the body from its ubiquitous precursor plasminogen under various physiological and pathological conditions, was also shown to be able to cleave VP 1 of polioviruses and bring about the corresponding modification of antigenic site 1. This observation extends the potential pathogenetic consequences of the host enzyme-mediated proteolytic modification of polioviruses from intestinal mucosa to most other tissues.