Transforming growth factors beta (TGF-beta) form a family of multifunctional polypeptides which in the active dimeric forms have a molecular weight of 25 kDa. Human glioblastoma cells secrete immunosuppressive TGF-beta consisting mostly of TGF-beta 2 rather than TGF-beta 1. The results shown here demonstrate that in addition to the mature 25 kDa form of TGF-beta 2, glioblastoma cells release a biologically active high molecular weight form of TGF-beta 2 which suppresses the interleukin-2-dependent growth of a T helper cell line. The high and low molecular weight forms of TGF-beta 2, separated by polyacrylamide gel electrophoresis under non-reducing conditions, can be eluted from the gel retaining their immunosuppressive activity. Similar results were obtained when analyzing supernatants of Chinese hamster ovary (CHO) cells transfected with a cDNA for TGF-beta 2. Both the high molecular weight form (90-120 kDa) and the 25 kDa form can be immunoprecipitated with a monoclonal antibody against mature native TGF-beta 2 and are detectable in tumor cyst fluid from glioblastoma patients. Taken together, the data provide evidence that in addition to the well-characterized 25 kDa form of TGF-beta 2 glioblastoma cells also secrete a high molecular weight form (90-120 kDa) with the biological characteristics of TGF-beta 2.