The arginine vasopressin (AVP) released from the hypothalamic slices containing paraventricular and supraoptic nuclei of Sprague-Dawley rats sectioned with vibratome and incubated in static microchambers was measured by radioimmunoassay, and the rapid effect and its underlying mechanism of glucocorticoids (GC) on AVP release were investigated. The results were as follows: (1) AVP was steadily released at a rate of 9.1 +/- 1.2 pg/min/well for as long as 6 h. (2) Corticosterone (B), within 20 min, inhibited AVP release in a dose-dependent manner from 10(-7) to 10(-4) mol/l. (3) Cortisol, 17beta-estradiol, or testosterone (all in 10(-6) mol/l) to some extent also inhibited AVP release, but dexamethasone, aldosterone, progesterone, RU 38486 or cholesterol had no significant inhibition on AVP release. (4) The rapid inhibitory effect of B was not affected by actinomycin D, puromycin or colchicine. (5) RU 38486 (10(-5)-10(-3) mol/l) could partially block the rapid inhibitory effect of B, although it did not by itself change AVP release. (6) With the elevation of Ca2+ in the incubation medium, the AVP release was increased and the rapid inhibitory effect of B enhanced; while in the absence of Ca2+ the AVP release decreased and the effect of B attenuated. (7) The rapid inhibitory effect of B was enhanced in the presence of neomycin, although the latter had no influence on AVP release. (8) Aminophylline did not affect the rapid inhibitory effect of B. These results indicated that the rapid inhibitory effect of GC might be a nongenomic rather than the classical genomic one, and that the extracellular Ca2+ play a role in the rapid effect of GC on AVP release. The significance of the rapid action of GC in the rapid negative feedback regulation of AVP release from hypothalamus of rats was discussed.