It has previously been shown that a approximately 27 kDa serine protease of Schistosoma mansoni larvae, the cercarial elastase (CE), was a poor immunogen in as much as it failed to induce an antibody response. The CE has a critical role in enabling schistosome larvae to penetrate the skin of their definitive hosts, so the apparently poor immunogenicity of this enzyme is clearly of interest. To understand its lack of immunogenicity better and in particular to determine whether it is related to its proteolytic activity, we have measured antibody responses of mice to three different serine proteases. Groups of mice were immunized with porcine pancreatic trypsin (TRY), chymotrypsin (CHY) or elastase (ELA) and the resulting antibody response compared with antibody responses to two non-protease antigens, chicken egg albumin (OVA) and Schistosoma japonicum glutathione S-transferase (GST), all being administered with alum as an adjuvant. Of 12 mice that were injected five times at 14 day intervals with TRY, only one produced antibody reactive with this enzyme in ELISA. Immunizations with CHY or ELA induced somewhat better antibody responses than TRY, but the responses to the first and second injections of these two proteases nevertheless seemed comparatively lower than the responses to GST. Induction of antibody responses by OVA and GST was not affected when TRY was injected concomitantly. Thus, the antibody response to one of the serine proteases used in this study, mammalian trypsin, was anomalous.