Abstract The development of the ability of insulin-induced hypoglycemia to cause reflex neuronally-mediated release of adrenal catecholamines was studied in rats exposed perinatally to methadone. In control rats, the response was absent at birth and developed by the first week of postnatal age. Rats whose mothers received daily injections of methadone showed precocious development of neonatal sympatho-adrenal responses, an effect which reflected earlier maturation of functional sympathetic innervation of the tissue. The developmental alteration caused by methadone was apparent even in rats withdrawn from drug at birth by cross-fostering to normal mothers; the effect also did not display a “critical period,” in that prenatal exposure alone produced the shift as well as did continuous exposure. Accelerated maturation of sympatho-adrenal function caused by methadone appeared to be independent of nutritional or body weight factors, and may represent a direct drug effect on the fetus or pup.