To examine the role of different immunoglobulin subclasses in the immune clearance of Trypanosoma cruzi, mice containing bloodstream trypomastigotes were injeeted intravenously with immune serum, IgG-depleted serum, or with thelgGI or IgG2 fraelionsand the rateof removal of the parasites from circulation was determined. Using IgG concentrations similar to those found in the immune serum, the rate of clearanee mediated by IgG2 was six-fold higher than that obtained with IgGI. This differenee did not appear to be due to differences in antibody specificity, as Western blotting showed that each isotype recognized a similar set of antigens extracted from the parasite. However, the T. cruzi specific antibody content of the IgG2 was approximately five-fold higher than IgG I - When the dose of IgG was adjusted to equalize the antibody content, the clearance ability of the IgGI and IgG2 was very similar. It is concluded Ihat the two subclasses have a similar clearance ability.