Percutaneous exposure of guinea-pigs to attenuated or normal larvae of Schistosoma mansoni induced proliferative T-cell responses in the skin-draining lymph nodes (SLN). The responses elicited by attenuated larvae were stronger and more prolonged [2-12 days post-infection (p.i.)] than those by normal larvae (3-8 days p.i.). The former were coincident with greater and more sustained increases in numbers of SLN dendritic cells. During this event, epidermal Langerhans' cells (LC) showed marked changes in their distribution and morphology. Resident LC were similarly exhausted by either attenuated or normal larvae between 12 hr and 1 day p.i., but thereafter more blood-borne LC were recruited around the former, since reaggregation of LC around these persisted larvae was more frequent and intensive, and enhanced replenishment of epidermal LC was achieved by 8 days p.i. When the skin depleted of epidermal LC by short-wavelength ultraviolet (UVC) irradiation was exposed to attenuated larvae, consequent T-cell responses were delayed. Excision of the whole exposed skin on day 4 p.i. also reduced T-cell responses to marginal levels. These results indicate that during the afferent phase of immunity to S. mansoni, efficient T-cell responses in the SLN need an active involvement of not only resident LC but also blood-borne LC as immunostimulatory cells.