To assess the role of peripheral sympathetic nerves in the regulation of parathyroid hormone (PTH) release rats subjected to bilateral superior cervical ganglionectomy (SCGx) 8-24 h earlier were used. SCGx did not result in significant changes of basal serum calcium (Ca) or immunoreactive PTH (iPTH) levels. The i.p. administration of EDTA every 30 min for up to 3 h brought about an impending decrease of serum Ca levels in both sham-operated and SCGx rats when assessed 23 h after surgery. The extent of hypocalcemia was significantly larger in the SCGx group. In sham-operated controls serum iPTH increased by 32-145%, 1-3 h after beginning EDTA treatment whereas such increases were considerably lower or absent in SCGx rats. In 3 out of 7 SCGx animals that survived to a double EDTA dose, iPTH increased to levels indistinguishable from controls. When SCGx rats subjected to surgery 23 h earlier and receiving d-1-propranolol (5 mg/kg) or phentolamine (10 mg/kg) 4 h and 30 min earlier were submitted to iterative EDTA injection serum iPTH increased, whereas no changes were detected in SCGx rats treated with vehicle and subjected to the same EDTA treatment. These data indicate that (1) SCGx does not affect basal release of iPTH or serum Ca concentration; (2) 23-26 h after SCGx there is a significant impairment of homeostatic iPTH responses to low Ca levels which can be overcome by suitable Ca stimulus; (3) circulating catecholamines may affect denervated parathyroid cells, as revealed by the changes in serum iPTH and Ca elicited by alpha- and beta-adrenoceptor-blocker treatment of SCGx rats.