The objective of this study was to examine the role of B cells in primary and challenge infections of larval Strongyloides stercoralis in mice. Two strains of B-cell deficient mice were used in these studies, microMT mice that lack all B cells and Xid mice that lack B-1 cells. Primary immune responses in microMT mice were sufficient to eliminate all parasites within 1 week after infection. Immunized microMT and Xid mice, however, were unable to kill challenge parasites at 24 h post infection, the time that they were eliminated in immunized wild-type mice. This was despite having a significant increase in interleukin-5 secreting cells and high numbers of eosinophils in the microenvironment of the challenge larvae. In addition, immunized Xid mice did not generate parasite-specific immunoglobulin (Ig)M but did develop a weak IgG response compared to wild-type mice. These results demonstrate a dichotomy in the requirement of B cells in immunity to S. stercoralis. B cells are not required in the primary response, yet they are required in the secondary immune response. B-1 cells are required for the secondary immune response and their role appears to be the production of IgM and not as a source of immunoregulatory molecules.