The T1/ST2 gene encodes, as a result of differential splicing, a cell surface protein (transmembrane form of T1/ST2, ST2L) and a soluble, secreted, protein (ST2). Here, we show that transcripts for both ST2L and ST2 are present in activated human Th2 clones, but not in Th1 and T regulatory clones. This activation-dependent expression of ST2L/ST2 transcripts was also found in short-term in vitro differentiated, activated CD4(+) Th2 cells. No expression of ST2L or ST2 mRNA was detected in any of the resting T cell subsets. Low cell surface expression of ST2L was detected on activated Th2 clones, and on freshly isolated non-IFN-gamma-producing CD4(+) peripheral blood T cells, activated with anti-CD3 and anti-CD28 mAb. Finally, ST2 could be detected in the culture supernatants of activated, but not resting, Th2 clones. Taken together, these results show that the T1/ST2 gene products are inducible proteins and that human Th2 cells, in addition to expressing ST2L at their cell surface, secrete ST2 following activation.