Abstract: BbKI is a kallikrein inhibitor with a reactive site sequence similar to that of kinins, the vasoactive peptides inserted in kininogen moieties. This structural similarity probably contributes to the strong interaction with plasma kallikrein, the enzyme that releases, from high-molecular weight kininogen (HMWK), the proinflammatory peptide bradykinin, which acts on B₂ receptors (B₂R). BbKI was examined on smooth muscle contraction and Ca²⁺ mobilization, in which the kallikrein-kinin system is involved. Contrary to expectations, BbKI (1.8 μm) increased [Ca²⁺]_cand contraction, as observed with BK (2.0 μm). Not blocked by B₁ receptors (B₁R), the BbKI agonistic effect was blocked by the B₂R antagonist, HOE-140 (6 μm), and the involvement of B₂R was confirmed in B₂R-knockout mice intestine. The same tissue response was obtained using a synthetic peptide derived from the BbKI reactive site structure, more resistant than BK to angiotensin I-converting enzyme (ACE) hydrolysis. Depending on the concentration, BbKI has a dual effect. At a low concentration, BbKI acts as a potent kallikrein inhibitor; however, due to the similarity to BK, in high concentrations, BbKI greatly increases Ca²⁺ release from internal storages, as a consequence of its interaction with B₂R. Therefore, the antagonistic and agonistic effects of BbKI may be considered in conditions of B₂R involvement.