The course of infection with Dipetalonema viteae in mice shows marked genetically-determined strain variation. Subcutaneous implantation of 5 female D. viteae into C57BL/10 (B10) mice results in a short term, low level microfilaraemia compared with that seen in similar infections in BALB/c mice. Adult worm survival is similar, thus the different patterns of infections reflect responses directed against the microfilariae larvae (mf). A number of immunological parameters have been monitored during infection in an attempt to identify strain differences which may be correlated with levels of resistance. Blast cell activity in the spleen and lymph nodes showed little strain difference, peaking on day 10 and declining as mf disappeared from the circulation. Total serum IgG levels doubled in both strains during infection, the response being more rapid in B10 mice. Serum IgM levels increased threefold in BALB/c mice but fourteen-fold in B10. Radiosorbent assays identified comparable anti-adult antibody and anti-mf homogenate IgM antibody responses in both strains. Immunofluorescent assay showed that the appearance of IgM antibodies directed against the mf surface correlated with the clearance of mf from the blood of B10 mice, whereas similar antibodies were not detected in BALB/c mice. It is proposed that the efficient clearance of mf in B10 is mediated through an IgM-dependent mechanism and that the chronic microfilariaemia seen in BALB/c mice is facilitated by the absence of a specific IgM response to mf surface antigens.