Transforming growth factor-β (TGF-β) binds to and signals via two serine-threonine kinase receptors, type I (TβRI) and type II (TβRII). The oligomerization of TGF-β receptors modulates ligand binding and receptor trafficking and may contribute to signal diversification. However, numerous features of the molecular domains that determine the homo- and hetero-oligomerization of full-length receptors at the cell surface and the mode of these interactions remain unclear. Here, we address these questions through computerized immunofluorescence co-patching and patch/fluorescence recovery after photobleaching measurements of different combinations of epitopetagged receptors and their mutants in live cells. We show that TβRI and TβRII are present on the plasma membrane both as monomers and homo- and hetero-oligomers. The homodimerization of TβRII depends on a cytoplasmic juxtamembrane region (amino acid residues 200-220). In contrast, the cytoplasmic domain of TβRI is dispensable for its homodimerization. TβRI·TβRII hetero-oligomerization depends on the cytoplasmic domain of TβRI and on a C-terminal region of TβRII (residues 419-565). TGF-β1 elevates TβRII homodimerization to some degree and strongly enhances TβRI·TβRII heteromeric complex formation. Both ligand-induced effects depend on the region encompassed between residues 200-242 of TβRII. Furthermore, the kinase activity of TβRI is also necessary for the latter effect. All forms of the homo- and hetero-oligomers, whether constitutively present on the membrane or formed upon TGF-β1 stimulation, were stable in the time-scale of our patch/FRAP measurements.Wesuggest that the different forms of receptor oligomerization may serve as a basis for the heterogeneity of TGF-β signaling responses.