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The isometric tension of anaphylactic guinea pig trachealis muscle preparation was examined at subphysiologic extracellular calcium concentrations, in vitro. Paired observations of control to passively sensitized (egg albumin antiserum) and antigen-challenged muscles (anaphylaxis) were made by exposure to trace Ca⁺⁺ followed by cumulative Ca⁺⁺ replacement. Following anaphylaxis, a leftward shift of the Ca⁺⁺ concentration-tension responses was found at 0.25–0.5 mM Ca⁺⁺ (p < 0.001); EC₅₀ was 1.5 × greater than control. A greater maximal tension was also noted at 2.52 mM Ca⁺⁺. Passively sensitized muscles did not exhibit this heightened response. Subthreshold tissue chemical mediators are tentatively excluded as causative. An increased sensitivity to extracellular Ca₊₊ exists in resting smooth muscle following anaphylaxis.