Marked enlargement of lymph nodes draining local skin reactions (chancres) occurred in sheep following intradermal inoculation of cultured metacyclic forms of Trypanosoma Congo Republiclense. Histologically, these lymph nodes were characterized by follicular hypertrophy and hyperplasia, compression and relative reduction of the paracortical areas and expansion of the medullary regions. Immunohistochemical staining with monoclonal antibodies to ovine lymphocyte subsets and Fc receptor (FeR) bearing macrophages, revealed increased expression of B cells (CD45R+), major histocompatibility complex (MHC) Class II, FcR+ macrophages, and CD1+ cells in the cortical and paracortical areas. The paracortical areas were found to be sparsely populated by CD5+, CD4+ and CD8+ cells, while the medullary areas contained numerous CD8+ cells and FcR+ macrophages. FcR+ macrophages were also present in cortical trabecular and subcapsular sinuses. As the chancre regressed, lymph node reactivity also subsided and fewer B cell follicles were observed and there was decreased expression of CD45R+ and MHC Class II+ cells.