C57BL6 mice were protected against Plasmodium berghei sporozoite challenge by immunization with live 12 krad dose-irradiated sporozoites, but not by 20 krad dose-irradiated sporozoites. Immunization with 12 krad irradiated sporozoites generated low levels of antibody reactive to liver-stage parasites (titres of 1/100). Inoculation of as few as 100 live P. berghei sporozoites induced complete host protection accompanied by a very quick and high boost of antibody titres up to 1/4000. This sporozoite challenge-drive antibody boost was absent in mice immunized by 20 krad sporozoites and in non-protected, and non-immunized mice. Antibody was mainly liver-stage (LS) specific and due to an increase of IgG2a and IgG2b. The in vitro effect of pre- and post-challenge sera upon either sporozoite invasion or LS development was assessed in Hep-G2 cultures. Both were found to have a strong effect upon LS development even at 1/2500 dilution, and conversely a low effect upon invasion. These results suggest that sporozoites irradiated at doses that induce protection are able to prime T-cells which, upon challenge by non-irradiated sporozoites, provide help to B-lymphocytes to trigger the production of high titres of anti-LS antibodies that can inhibit LS development in vitro.