It was possible to block the transmission of an infection of a rodent malaria parasite Plasmodium yoelii nigeriensis to Anopheles stephensi mosquitoes by immunising mice with a vaccine containing formalin-fixed gametes. A single dose of the gamete vaccine containing 2x106 male gametes given intravenously was effective in blocking completely the transmission of a blood induced challenge infection. The vaccine was also effective when given intramuscularly and immunity was found to last at least six months. Transmission blocking immunity was found to reside in a serum factor, probably antibody, and to be directed against extracellular gametes, acting on them in the gut of the mosquito while gametocytes in the circulation of the vertebrate host remained unaffected. A limited study involving experimental vaccination with formalin-fixed erythrocytic parasites was also undertaken. A crude erythrocytic stage vaccine protected mice against the asexual blood stages of a challenge infection and protection was found to be enhanced by killed Bordetella pertussis organisms used as an adjuvant. The gamete vaccine afforded partial protection against the disease. Immunisation with asexual parasites alone showed that this protection was due to the presence of asexual forms as contaminants and that anti-gamete immunity is stage specific. Factors affecting the infectiousness of gametocytes in a natural infection were also investigated. It was found that mice elaborate anti-gamete immunity in response to an infection which renders it non-infectious to mosquitoes after about the fifth day. In addition, gametocytes display a pattern of altered viability during the course of an infection where they lose the capacity to exflagellate. The possibility of this being either a manifestation of an intrinsic cycle of gametocyte development or immunity mediated by non-specific non-antibody factors that affect gametocytes within red cells is discussed.