Mice genetically selected for high (Ab/H) or low (Ab/L) humoral antibody responses were infected with Schistosoma mansoni in order to assess the role of antibodies in innate and acquired immunity to this parasite. AbH mice produced higher levels of humoral antibodies to schistosome antigens, but were more susceptible to infection than Ab/L mice. This was shown by the higher number of parasites recovered from Ab/H mice, by the larger size of the parasites themselves, by the number of schistosome eggs and their rate of deposition in the host liver. In addition, Ab/L mice could develop an acquired resistance to schistosome re-infection which was as good as, or possibly even better than the resistance developed by Ab/H mice. These findings suggest that humoral antibodies per se may not play a critical role in schistosome immunity, and at the same time call attention to the possible importance of macrophages in determining the results observed.