The migration of isotopically labelled Schistosoma mansoni challenge cercariae was monitored, by means of squashed organ autoradiography, in naive Sprague-Dawley rats and rats protected with serum harvested from twice vaccinated donors. The majority of challenge larvae migrated from the skin to the lungs in both groups of rats, but a significantly increased number of larvae was retained in the lungs of serum recipients on day 8 post-challenge. An average of 25% of the challenge population succeeded in migrating to the livers of naive rats by day 14, compared to only 13% in passively protected animals; serum recipients were shown by perfusion on day 21 to be 73% immune. Histological examination of lung tissue harvested from naive rats challenged intravenously with lung-stage schistosomes revealed small foci composed of mononuclear cells that sometimes enclosed larvae; these worms are likely to be lost due to innate resistance. In the lungs of serum-protected rats, many challenge larvae were seen to be surrounded by extensive eosinophil-enriched inflammatory foci; parasite remnants were also observed within such reactions. Ultrastructural examination of worms recovered from the lungs of passively protected animals revealed muscle disruption and internal vacuolation, although the tegument remained intact. It is proposed that challenge attrition in serum-protected rats occurs essentially in the lungs and involves larval immobilization and subsequent death, perhaps mediated by cellular mechanisms.