The human B 1 bradykinin receptor is an inducible and constitutively active G protein-coupled receptor that is involved in the inflammatory and pain responses to injury. Here, we investigated the role of B 1 receptor homo-oligomerization in cell surface receptor expression. B 1 receptors tagged with either the FLAG or hemagglutinin epitope were monitored immunologically and by radioligand binding, biotinylation, and phosphoinositide hydrolysis in human embryonic kidney 293 cells. Selective immunoprecipitation, immunoblotting, and immunoelectron microscopy with epitope-specific antibodies together provided evidence for constitutively formed cell surface receptor homo-oligomers. Truncation of the receptor from the N-and C-terminal ends indicated that the epitope for oligomerization seems to be located between Leu 26 on top of transmembrane helix 1 and Val 71 at the bottom of helix 2. A receptor construct terminating at Asp 134 at the bottom of helix 3, B1stop135, was expressed in the cell. It is interesting that this construct behaved as a dominant-negative mutant by competitively preventing formation of intact B 1 receptor homo-oligomers, and redistributing B 1 receptors from the cell surface to a common intracellular compartment. In contrast, expression of a construct containing the residues downstream of Asp 134 , B1del(2-134), was inactive in this regard. Together, these results are consistent with a mechanism where constitutive B 1 receptor homooligomerization is required for expression of receptors on the cell surface and subsequent constitutive receptor signaling. This may be a novel mechanism by which the cell regulates the presentation of this constitutively highly active receptor at various stages of injury.