A model of human hookworm infection has been developed which shows that dogs currently infected with small numbers of hookworms are considerably resistant to a challenge infection with a large inoculum of infective larvae. Two groups of dogs were infected with 500 larvae and four weeks after infection one group together with a previously uninfected control group were infected with 5,000 larvae and followed for six weeks. When compared with the secondary infection control dogs, faecal egg excretion and adult worm burdens were reduced by an average of 83 and 78% respectively. Infections had no significant effect on total white cell counts, platelet levels or spontaneous, phytohaemagglutinin- and antigen-induced lymphocyte transformation among the three groups of dogs. Dogs previously uninfected with hookworm developed a marked anaemia when infected with 5,000 larvae but this was not observed in the superinfected group. An eosinophilia developed in all groups and there were no significant differences among the three groups of animals. Specific IgM antibodies developed transiently in all groups of dogs two weeks after infection. IgG antibody levels were significantly greater in the superinfected animals one, two and three weeks after challenge infection compared with the secondary infection control animals; by four weeks there was no significant difference between the two groups of animals. Both groups given the large inoculum of larvae developed specific IgA antibodies one week after the challenge infection and these continued to rise in the superinfected group until termination of the experiment. It is concluded that dogs currently infected with the hookworm, Ancylostoma ceylanicum, demonstrate the development of functional protective immunity.