A single large dose (200 mg) of cyclophosphamide (Cy) given to adult rats caused a drastic depletion of lymphocytes occurring earlier in the B dependent compartment than in the T dependent one of the lymph node cortex. The drug had a somewhat facilitating effect on the early differentiation of plasma cells (between 12 and 24 h) which later were also depleted. By Cy administration two types of macrophage were distinguished morphologically and topographically in the lymph nodes. Cy effect the endothelial cells lining the blood vessels and lymph sinuses. From day 4 to 7 Cy caused a constant flooding of red blood cells into the lymph node sinuses like in the normal rat haemolymph gland. Regeneration of the mesenteric lymph nodes occurred by a repopulation of lymphoid cells and a proliferation of other cell types. Repopulation of the B dependent compartment lagged behind that of the T dependent compartment. Regeneration of endothelial cells seemed to be one of the factors facilitating the repopulation of lymphoid cells. The distribution of T and B dependent cells in different compartments of the rat lymph node and activation of mononuclear phagocytes in Cy treated rat lymph node are discussed.