Prior studies indicate that a microfilarial stage-specific chitinase is a possible candidate antigen for a transmission-blocking vaccine against Brugian filariasis. The antigen is a functional enzyme that progressively appears as microfilariae mature and become able to infect and develop in a susceptible mosquito vector. It is recognized by a monoclonal antibody that reduces microfilaremia in infected animals and by a subset of sera from infected persons who remain amicrofilaremic. Immunization of jirds with recombinant chitinase induced partial protection against microfilaremia resulting from subsequent infection with Brugia malayi, but did not reduce adult worm burdens. Vaccination was much less effective when administered during the prepatent stage of infection and was ineffective when given to microfilaremic jirds. The protective epitope appears to be located close to the carboxy terminus of the chitinase molecule. Immunization of jirds with SXP1, an antigen present in multiple worm stages, also reduced microfilaremia and, in some experiments, adult worm burdens, but hyperimmunization with a recombinant filarial myosin was not protective. These observations indicate that the relative timing of immunization and infection is an important factor in the efficacy of antimicrofilarial vaccines.