The cellular responses in regional lymphoid organs of C57B1/6 mice were examined, following protective immunization with 20 krad.-irradiated cercariae of S. mansoni. Marked changes in total cell number were observed, with peak increases of 13.5-fold in the skin-draining (axillary) lymph nodes and 6.9-fold in the lung-draining (mediastinal) lymph nodes. In contrast, cellular responses were small in the spleen and undetectable in the brachial lymph nodes. The temporal pattern of responses was coincident with the kinetics of parasite migration, events in the mediastinal lymph node being apparent only after day 7. Phenotypic analysis of the cellular changes revealed an increase both in T lymphocytes and, to a greater extent, in B lymphocytes. The changes in Thy1+ cells comprised an increase in both L3T4+ and Lyt2+ populations. A comparison of mice exposed to non-immunizing parasites (normal or 80 krad.-irradiated cercariae) with protected animals, revealed smaller and more transient cellular changes in the axillary lymph nodes of the former. We suggest that the successful immunization of mice with attenuated parasites depends upon the prolonged priming of lymphocytes within the lymph nodes draining the skin-exposure site and that the persistence of 20 krad.-irradiated parasites within these nodes provides the requisite stimulus.