Summary: Using an in vitro tissue incubation technique, the capabilities of mouse thoracic duct cells to synthesize immunoglobulins was compared to those of solid lymphoid tissues. Spleen and lymph nodes made all four classes of immunoglobulins and the ileum and jejunum only IgA. Thoracic duct cells synthesized IgA and IgM, but no 7 S γ1 or 7 S γ2. Cells obtained from the 1st day produced less IgA and IgM than those collected from later days. The amount of immunoglobulins synthesized by thoracic duct cells appeared to be less than that by equal samples of spleen cells. These studies suggest that thoracic duct cells are not, in general, representative of the lymphoid population. Culture of tissues obtained from chronically drained animals yielded autoradiographs similar to normal patterns for each organ. Thus cells synthesizing each of the immunoglobulin classes remained fixed in tissues and were not removed from the animal. The lymph contained relatively large amounts of 7 S γ1, 7 S γ2 and IgA; the serum levels of these were rapidly lowered with drainage. Very small quantities of IgM were present in the lymph and prolonged drainage was necessary to decrease its serum level. Therefore, thoracic duct drainage diminishes the serum immunoglobulin levels partly by direct protein loss and partly by removal of the cells or their precursors responsible for synthesis.