Effects of dexamethasone on development of sympathetic nerve function in the heart were evaluated by giving 1 mg/kg of dexamethasone s.c. daily for several days beginning the day after birth. Dexamethasone interfered with tyramine- and isoproterenol-induced tachycardia in the neonates but did not cause alterations in development of a marker for presynaptic sympathetic nerve terminals (synaptic vesicle uptake of [3H] norepinephrine) nor of postsynaptic beta adrenoceptor binding of [3H]dihydroalprenolol; the deficit was also unrelated to general cellular effects of the hormone. These data suggest that the subnormal chronotropic responses of the heart to sympathetic stimulation in dexamethasone-treated neonatal rats result from uncoupling of receptors from the organ response. The effects of dexamethasone on cardiac responses were specific to the neonate, as mature rats given dexamethasone did not show suppression of cardiac sympathetic action. Neonatal dexamethasone treatment also produced a deficit of adrenomedullary development with deficiencies in catecholamine levels and in catecholamine biosynthetic enzymes; deficits in phenylethanolamine N-methyltransferase activity persisted into young adulthood.