The production and the circulation of lymphocytes has been examined in the sheep fetus where neither foreign antigen nor immunoglobulins occur. It was found that as the lymphoid organs increased in size during fetal life, the numbers and the output of lymphocytes in the thoracic duct lymph increased. The recirculating pool of lymphocytes was estimated to be 5.5 +/- 1.5 X 10(8) cells in fetal lambs 95-100 days of age, 5.7 +/- 1.2 X 10(9) cells in fetuses 130-135 days of age, and 1.2 +/0 9.3 X 10(10) cells in fetuses near to term. The rate of addition of lymphocytes to the recirculating pool was 3.2 +/- 1.9 X 10(6) cells/h in fetuses of 100 days and 3.4 +/- 0.9 X 10(7) cells/h in fetuses of 130 days of age. Lymphocytes recirculated from blood to lymph in fetuses; labeled cells injected into the blood stream reappeared in the thoracic duct lymph promptly and reached maximum levels around 12-18 h after they were injected. Labeled lymphocytes were detected subsequently in greatest numbers in the lymph nodes, particularly in the mesenteric lymph nodes and in the interfollicular areas of the Peyer's patches. Chronic drainage of thoracic duct lymph from fetuses in utero for periods of up to 36 days had no obvious effects on the growth or development of the fetus and only minimal effects on the content of lymphocytes in the various lymphoid tissues even though the number of cells in the blood and lymph were reduced to between 20-30% of normal levels. Thymectomy done in fetuses about 2 mo befor cannulation of the thoracic duct reduced the output of cells in the thoracic duct to about 25% of normal levels and caused a significant reduction in the content of lymphocytes in the various lymphoid tissues. Thymectomized fetal lambs subjected to thoracic duct drainage for periods up to 2 wk in utero had a similar complement of lymphocytes in their lymphoid tissues to intact thymectomized fetal lambs. Lymphocytes obtained from the thoracic duct lymph of lambs thymectomized 2 mo previously recirculated from blood to lymph when they were injected intravenously, although they did this at a significantly slower rate than did lymphocytes from normal lambs.

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