Extracts from lymph node and spleen in mice and rats subjected to restraint stress significantly suppressed lymphocyte proliferation, but extracts from brain, skeletal muscle, and thymus gland had no effect on lymphocyte proliferation, suggesting that a suppressive factor for lymphocyte proliferation might selectively be induced in lymph node and spleen. Further experiments showed that biochemical properties, molecular weight, correlation between suppressive factors in serum and in extract of the lymph tissue from stressed animals, and control of the generation, all indicated that under the conditions of restraint stress and under the control of central nervous system a suppressive factor was generated in peripheral lymph tissue and then released into the blood-stream, which acted as a strong suppressor of lymphocyte proliferation.