Using histochemical ATPase-staining of the guinea pig epidermal sheet, we have demonstrated remarkable accumulations of ATPase-positive cells after exposure to attenuated Schistosoma mansoni cercariae. To characterize further the cells accumulating in the skin after exposure to S. mansoni, we produced a panel of monoclonal antibodies (MAb) to guinea pig leukocytes. These were immunohistochemically classified into 15 types and included MAb to the major histocompatibility complex (MHC) Class I and Class II molecules, shared antigens of all lymph node cells or between lymph node cells and Langerhans' cells (LC), T cells and macrophages (M phi), and M phi including the large Tingible body M phi in the secondary follicle. Varied MAb to M phi, including commercially available MAb (MR-1), were negative with ATPase- and MHC Class II-positive cells accumulated in the skin exposed to S. mansoni. Three MAb (HUSM-30 and 46, and commercially available MSgp2) detected an identical staining profile of accumulated cells with epidermal LC, but two MAb (HUSM-12 and 42) positively stained accumulated cells but not resident LC. These results indicate that the cells accumulated in the guinea pig skin within a few days after exposure to attenuated cercariae of S. mansoni are closest to LC, not to Mø, and may be blood-borne LC/dendritic cells.