Short-term desensitization of the contractile response of the guinea-pig taenia caecum to histamine was tested in the absence of Ca++. Desensitization was monitored both by the fall of histamine response and by the decrease of irreversible blockade by phenoxybenzamine. In Ca++-free solution with 0.2 mM EGTA, desensitization occurred as in normal physiological solution containing Ca++.