Effects of postnatal sympathectomy on inotropic responsiveness to alpha-adrenoceptor stimulation were examined in mouse myocardia to determine whether the developmental conversion of alpha-adrenoceptor-mediated inotropic responses from positive to negative is triggered by sympathetic innervation. Sympathectomy was performed chemically by consecutively administering 6-hydroxydopamine for 14 days after birth and confirmed by the absence of inotropic responses to tyramine. In newborn myocardia, phenylephrine, in the presence of propranolol, produced concentration-dependent positive inotropic responses. Three weeks after birth, phenylephrine, in the presence of propranolol, produced concentration-dependent negative inotropic responses, both in control and in sympathectomized myocardia; no difference was observed between the two groups of mice in the maximum decrease in contractile force produced by phenylephrine. The sensitivity (pD2 value) to phenylephrine was significantly higher in sympathectomized myocardia. In conclusion, sympathetic innervation of the mouse ventricular myocardium is not required for the developmental conversion of the alpha-adrenoceptor-mediated inotropic response from positive to negative.