The effect of [Asu1,7]eel calcitonin (ECT), an equipotent analogue of eel CT, on prolactin (Prl) secretion was examined in 12 healthy male subjects and in 6 patients with prolactinoma. In healthy subjects, ECT (0.5 microgram/kg body weight . h) or saline was infused for 2 h and TRH was injected iv as a bolus of 500 micrograms at 1 h of ECT or saline administration. ECT did not affect basal Prl levels during 1 h of infusion. TRH caused a significant increase of plasma Prl with peak values of 75.2 +/- 11.6 ng/ml in ECT-infused subjects, which did not differ from those infused with saline (68.5 +/- 8.3 ng/ml). Next, an iv bolus injection of regular insulin (0.1 U/kg body weight) was followed by an infusion of ECT or saline alone. Plasma Prl peaks after hypoglycaemic stress were significantly lower in ECT-infused subjects than those in saline-injected controls (ECT, 16.5 +/- 3.1 vs 33.5 +/- 9.6 ng/ml, P less than 0.05). In patients with prolactinoma, basal levels of plasma Prl ranging from 42.0-4130 ng/ml failed to change during iv infusion of ECT. Moreover, ECT (10(-9) - 10(-6)M) did not affect Prl release from prolactinoma tissues perifused in vitro. These findings suggest that ECT may not act directly on the pituitary to modify Prl release. Rather, peripherally administered ECT appears to suppress Prl release via the central nervous system.