Expression systems have been designed to test the suitability of expressing the high cysteine containing extracellular domain (residues 1-136) of human transforming growth factor beta type II receptor (T beta RII), Receptor expressed using a baculovirus system was functional following both enzymatic deglycosylation and elimination of the N-terminal 22 amino acids by protease degradation. Bacterial expression of a T beta RII lacking the 26 N-terminal amino acids retained the ability to bind its ligand, TGF-beta 1. Receptor expressed in bacteria was sensitive to proteolytic degradation at residue Lys98 but a K98T mutation eliminated degradation and did not disrupt binding. Although several different forms of T beta RII were expressed, only a fusion with glutathione S-transferase gave soluble T beta RII, which was purified at a yield of 0.1 mg/10 L of bacterial growth. N-Terminal truncations of T beta RII (residues 22-136 or 27-136) could be refolded from inclusion bodies and purified to an active form with an efficiency of 10%.