A cysteine proteinase (SMw32) from the digestive tract of an adult Schistosoma mansoni worm has previously been purified and characterized. During the course of infection with this parasite, a strong immune response to the enzyme occurs. We now have confirmed the presence of anti-proteinase IgE and IgG in S. mansoni infected mice and have investigated the in vivo cellular response to proteinase in infected and uninfected mice. Immediate and delayed type hypersensitivities were detected in uninfected mice sensitized by multiple injections of proteinase. In S. mansoni infected mice, immediate hypersensitivity reactions were seen at 6 and 8 weeks following infection, coincident with the increase in anti-proteinase IgE antibody. Histological sections of the injection site confirmed the presence of degranulating mast cells. In contrast, delayed type hypersensitivity could not be detected at any time during the course of the infection. In the murine model of acute infection, immediate hypersensitivity to the SMw32 proteinase was predictive of infection.