The results presented here point to the possibility that calf thymus extracts contain, in addition to the thymic hormone (THF), a second component: thymic plasma recirculating factor (TPRF). THF, which is involved in the process of T cell maturation and has been characterized as a protein of m.w. 3000 eluted in the void volume of a G-10 Sephadex column (G-10-I), caused an increased level of intracellular cAMP in umbilical cord blood lymphocytes (UCBL). This is in agreement with our previous observation that THF plays a major role in the differentiation of T cells. The second active material, TPRF, also isolated from thymic extract, is of a molecular size below 500 and was eluted in a G-10 Sephadex column at the fourth protein peak; it seems to circulate in the blood. Previously, we had observed in impaired response of UCBL to PHA and Con A stimulation in the presence of dialyzed human plasma (DHP). Our present results indicate that this impaired response is restored exclusively by TPRF. A factor with TPRF-like activity was also isolated from the plasma of normal donors; yet it was not detected in the plasma of thymectomized patients suffering from myasthenia gravis (MG). This suggests that TPRF from plasma is thymus dependent. TPRF does not affect the level of intracellular cAMP in UCBL.