Laboratory rodents vaccinated with highly irradiated cercariae of Schistosoma mansoni develop significant levels of specific acquired resistance yet effect challenge elimination in different organs. Mice and guinea-pigs are at opposite ends of the spectrum in this respect since, in our hands, vaccinated mice kill challenge parasites in the skin whereas vaccinated guinea-pigs kill challenge parasites predominantly in the liver. To determine whether this phenomenon is host-dependent (site) or parasite-dependent (stage), we have transferred worms harvested from mice or guinea-pigs into vaccinated recipient guinea-pigs. The results show that mouse-derived 5-day lung worms and 9-day liver worms that are essentially refractory to vaccine resistance in mice are indeed susceptible to vaccine resistance in guinea-pigs. Identical levels of susceptibility were recorded for lung-stage larvae introduced via the foot vein so as to experience lung and liver mechanisms, or via the mesenteric vein to bypass the lung, thereby confirming that vaccine resistance in guinea-pigs operates in the liver. Mouse worms and guinea-pig worms exhibited equivalent levels of susceptibility at all stages of development. Thirteen-day-old larvae from either donor species were on the border-line of vulnerability, while 20-day-old worms were totally refractory to vaccine immunity in guinea-pigs. These data show that vaccine immunity in different rodent species is a site-dependent, rather than a stage-dependent phenomenon. There is, however, an upper age limit of schistosome vulnerability which is common to worms harvested from different donor species.