We have characterized the T lymphocyte population of the human neonate in respect of the expression of phenotypic profiles for naive, memory and differentiated populations. We have examined the response of the neonate T cell to the superantigen Staphylococcus enterotoxin B (SEB) and compared the response to T cells from healthy adults. We found that the primary response to SEB is equivalent in neonates and adults but that the secondary response demonstrates hyporesponsiveness in the neonate that is more profound than in adults. This response was associated with increased expression of CD25; the alpha chain of the IL-2 receptor, equivalent to that seen in responding cells from adults. A modest increased expression of CD122 and CD132, the beta and gamma chains of the IL-2 receptor, was also observed. There was no increase in the IL-4 receptor (CD124). The hyporesponsive neonate T cells proliferated in response to exogenous IL-2 but the response was less than none SEB treated cells. The neonate cells did not respond to IL-4. We also examined the expression of MHC class II molecules on SEB stimulated cells and found that both neonate and adult T cells upregulate MHC class II to a similar degree. The difference in the hyporesponsive cells appears to result in part from a lower production of IL-2 and in part from a lower ability of cord cells to respond to IL-2. Since the stimulated cord cells expressed IL-2 receptor at the same levels as similarly treated adult cells; there may be differences in down stream signaling pathways.