Sera from donors exposed to malaria were tested for their ability to block the transmission of isolates from Cameroonian Plasmodium falciparum gametocyte carriers. Sera were selected from amongst Cameroonian and Gambian donors who had positive antibody reactivity against the surface of activated gametes and against epitopes of Pfs 48/45 (a potential transmission-blocking vaccine candidate antigen). Aliquots of washed blood from gametocyte carriers were resuspended in test and control sera and fed to An. gambiae mosquitoes via a membrane feeder. Comparisons of the prevalence and intensity of infections in dissected mosquitoes showed variations in the ability of sera to block the transmission of the different isolates. Sera were identified that had little or no blocking effect on the transmission of isolates unless the isolate was poorly infectious. Some sera completely blocked the transmission of some isolates whilst having little or no effect on others. The observed variation in transmission-modulating activity may have implications for the development of a transmission-blocking vaccine.