Indirect immunofluorescence of Schistosoma mansoni adult worm sections has revealed that the early immunoglobulin response is directed toward the parasite digestive tract. One of the components of the worm gut is a cysteine proteinase which degrades host hemoglobin ingested by the parasite. In this report the purified proteinase (SMw32) was used in ELISA and immunoblot analyses to study the specific antibody response during the course of an acute infection. We have found high titer IgG antibody in S. mansoni infected, but not uninfected, mice. The anti-proteinase response involves IgM, IgG1, IgG2a, and IgE isotypes. Total IgM and IgG levels increased by week 3 post-infection and remained elevated throughout the study (7 weeks). Increased titers (IgM, IgG) of specific anti-proteinase were also apparent by week 3 post-infection, long before fecal eggs were detectable. Mean anti-proteinase IgG stabilized at high titer by week 5 post-infection, while IgM titers decreased to near background levels. Anti-proteinase IgE was first detectable at week 4 and reached peak titers by weeks 6 and 7. The strong antibody response to the purified SMw32 proteinase is consistent with the early reactivity of S. mansoni infected mice and humans to a 31 kDa component of the worm gut described by others.