The activity of spleen, mesenteric lymph nodes, femoral lymph nodes, thymus, bone marrow, blood and thoracic duct lymphoid cells from Balb/c mice in producing graft-vs-host reactions when grafted to newborn C57BL/6 recipients was compared quantitatively using the Simonsen spleen assay. Blood and thoracic duct lymphocytes were more than four times as active as spleen cells. Spleen cells from mice drained of lymphocytes from the thoracic duct were less than 50% as active as normal spleen cells. Mesenteric lymph node cells were slightly less active than spleen cells. Femoral lymph node cells produced splenic enlargement intermediate between that produced by circulating lymphocytes and spleen cells. However, inocula of femoral node cells in excess of 2 × 106 produced early runting (by day 9 after grafting) in 100% of recipients. This capacity to produce wasting was found in no other cell population examined. Thymus cells were only 15% as active as spleen cells, and bone marrow cells produced no early splenic enlargement in recipients. The results are interpreted as indicating (a) that the GVH activity of the spleen and probably of several other solid lymphoid tissues is accounted for by their content of lymphocytes from the circulating pool, and (b) that the femoral nodes contain a high proportion of cells qualitatively different in producing GVH reactions from those in other tissues.