We hypothesized that the inducible kinin B₁ receptor (B₁R) is rapidly cleared from cells when its synthesis subsides. The agonist-independent degradation of the rabbit B₁Rs and related B₂ receptors (B₂Rs) was investigated. Endocytosis of the B₁R-yellow fluorescent protein (YFP) conjugate was more intense than that of B₂R-green fluorescent protein (GFP) based on fluorescence accumulation in HEK 293 cells treated with a lysosomal inhibitor. The cells expressing B₁R-YFP contained more GFP/YFP-sized degradation product(s) than those expressing B₂R-GFP (immunoblot, antibodies equally reacting with both fluorescent proteins). The binding site density of B₁R-YFP decreased in the presence of protein synthesis or maturation inhibitors (anisomycin, brefeldin A), whereas that of B₂R-GFP remained constant. Wild-type B₁Rs were also cleared faster than B₂Rs in rabbit smooth muscle cells treated with metabolic inhibitors. Contractility experiments based on brefeldin A-treated isolated rabbit blood vessels also functionally support that B₁Rs are more rapidly eliminated than B₂Rs (decreased maximal effect of agonist over 2 h). The highly regulated B₁R is rapidly degraded, relative to the constitutive B₂R.