Experimental evidence was sought to support or oppose the hypothesis that resistance of rabbits to primary infection with Obeliscoides cuniculi is immunologically mediated. Treatment of infected rabbits with cyclophosphamide resulted in a decreased serological response to a test antigen, conalbumin, and a concomitant increase in worm burdens, worm maturity, and worm length on infection days 13 to 14. Serum from rabbits undergoing high-level 0. cuniculi infection conferred passive immunity to cyclophosphamide-treated rabbits with low-level infection, as evidenced by decreased worm burdens in the serum recipients. A passive hemagglutination study showed that rabbits were able to respond serologically to high-level infection within 2 weeks. This evidence supports the contention that resistance to primary low-level 0. cuniculi infection is due, at least in part, to an acquired immunological response, and that resistance to high-level 0. cuniculi infection in the rabbit is partly mediated by antibody produced in response to infection. Resistance to nematode parasitism arising from previous exposure to the homologous species of parasite is a well-known phenomenon. A probable immunological component of resistance has been demonstrated by passive transfer of immunity to the following species: Nippostrongylus brasiliensis (Sarles and Taliaferro, 1936), Strongyloides ratti (Lawler, 1940), Trichinella spiralis (Culbertson, 1942), Dictyocaulus viviparus (Jarrett et al., 1955), Ascaris suum (Kelley and Nayak, 1965), Ancylostoma caninum (Miller, 1967), and Aelurostrongylus abstrusus (Hamilton, 1968). In addition, adoptive transfer of immunity with lymphoid cells has been accomplished with T. spiralis (Larsh et al., 1964), Trichostrongylus colubriformis (Wagland and Dineen, 1965), and A. caninum (Miller, 1967) infections. Decreased resistance following immunosuppressive treatments of hosts with drugs, surgery, ionizing radiation, or antilymphocyte serum is also an indication of the immunological nature of such resistance. Dunsmore (1961) decreased delayed development of Ostertagia spp. in sheep by treating the hosts with cortisone or whole-body beta irradiation. Soulsby and Owen (1965) treated trichostrongyle-infected sheep with the alkylating agent chlorambucil and some of the treated animals responded with Received for publication 31 March 1970. * This work was supported by Medical Research Council of Canada grant MA-3070 and a Principal's National Research Council grant to A.E.S. increased fecal egg output. Ritterson (1968) demonstrated a marked increase in the susceptibility of Chinese hamsters to T. spiralis during treatment with the antifolate drug methotrexate. Resistance of rats to N. brasiliensis has been lessened by thymectomy (Ogilvie and Jones, 1967) and administration of antilymphocyte serum (Kassai et al., 1968). Obeliscoides cuniculi is a nematode which undergoes the parasitic phase of its life cycle entirely within the rabbit's stomach (Sollod et al., 1968). It was used in the present study as a model for the investigation of resistance mechanisms to trichostrongylid infections. Resistance to primary infection was demonstrated and evidence was sought to support or oppose the hypothesis that this resistance was immunologically mediated. MATERIALS AND METHODS Male New Zealand white rabbits served as experimental hosts. They were 6 to 8 weeks old and had an average body weight of 1.65 kg at the beginning of each experiment. All rabbits were obtained from a single breeding colony (University of Saskatchewan, Medical Research Annex) and were assigned to experimental groups with the aid of a random numbers table. Contaminating helminth infections were not detected by fecal flotation examinations or by necropsy. 0. cuniculi was maintained in the laboratory by periodic passage in New Zealand white rabbits. The production and storage of infective larvae has been previously described (Sollod et al., 1968). Rabbits were inoculated by gastric intubation. The appropriate volume of the larval suspension was determined by counting the number of larvae in