Recent evidence suggests that of calcitonin (CT) and parathyroid hormone (PTH) is controlled by factors other than the ambient serum calcium concentration. We studied the effects of infusions of four neuroendocrine modulators upon CT and PTH levels: isoproterenol (beta-adrenergic agonist), methoxamine (alpha adrenergic agonist), prostaglandin E2, and somatostatin. Isoproterenol was a consistent secretagogue for both hormones. Maximal CT increments during isoproterenol infusion in normal subjects were 13 +/- 2 pg/ml (mean +/- SEM, n = 6, P less than 0.001; basal, 26 +/- 5). Maximal increments in PTH were 113 +/- 22 pg/ml (P less than 0.01, n = 6; basal, 430 +/- 11). Infusions of methoxamine increased CT by 13 +/- 5 pg/ml (n = 5, P less than 0.05; basal, 43 +/- 13), but had no effect on PTH. The means of the maximal CT increments during isoproterenol (21 +/- 8 pg/ml) and methoxamine infusion (28 +/- 11 pg/ml) were not statistically different from those achieved by acute elevations of serum calcium levels within the physiological range (41 +/- 23 pg/ml). Infusions of somatostatin and prostaglandin E2 had no or only transient effects on basal or stimulated CT or PTH levels. Our data suggest that adrenergic input modulates CT and PTH secretion in humans independently of changes in serum calcium.