1. Desensitization of contractile responses dependent on release of intracellularly stored Ca elicited by carbachol, histamine or caffeine was measured after desensitizing treatment with carbachol or histamine in the presence or absence of local anaesthetics in Ca-free solution containing 2 mM EGTA in the smooth muscle of guinea-pig taenia caecum. 2. Histamine-induced homologous desensitization was inhibited by tetracaine and procainamide. Dibucaine did not exert an inhibitory effect on the desensitization. This is consistent with our previous findings concerning the effects of local anaesthetics on the desensitization of histamine H1-receptors measured under normal physiological conditions. 3. Carbachol induced a functional change of intracellular Ca stores which resulted in heterologous desensitization. Tetracaine completely blocked carbachol-induced desensitization of the caffeine-elicited contraction, but in the case of carbachol-induced desensitization of carbachol- and histamine-elicited contractions, this blocking effect of tetracaine was very weak and absent, respectively. The other local anaesthetics used did not affect the desensitization. These results suggest that the Ca-induced and inositol trisphosphate-induced Ca release mechanisms were both desensitized by carbachol and that the desensitization of the Ca-induced Ca release mechanism was selectively blocked by tetracaine.