Hybridoma clones producing IgM naturally occurring (natural) antibodies were generated from naive Balb/c mice and characterized for reactivity against parasite antigens. Ascites of mice injected with these hybridomas reacted with Toxoplasma gondii soluble antigen at levels approximately 1000–10000 times higher than serum pooled from mice used for generating hybridomas as determined by a conventional enzyme-linked immunosorbent assay. Western blot analysis indicated that these monoclonal antibodies reacted with multiple antigen molecules of T. gondii with patterns similar to that of pooled mouse sera. These antibodies also reacted with multiple antigens of Plasmodium yoelii, Entamoeba histolytica, Ascaris lumbricoides, Toxocara canis, Trichuris vulpis, Fasciola hepatica, Schistosoma mansoni, and Dipylidium caninum. When one monoclonal antibody was absorbed with these parasite antigens, its reactivity with T. gondii antigen molecules was consistently reduced, independent of parasite species. These natural antibodies failed to kill T. gondii tachyzoites in vitro or to protect mice from lethal challenge with T. gondii. These results indicate that natural antibodies detected in sera of naive mice are secreted from certain B cell populations and that these antibodies are multireactive with parasite antigens and have low affinity.