The prejunctional effects of angiotensin II (AII) on stimulation-evoked secretion of3H-norepinephrine (3H-NE) were investigated byin vitromethods in isolated, superfused rabbit iris-ciliary body preparations. AII (0.1–10 nM) concentration-dependently enhanced the field- stimulated release of3H-NE (EC50 = 0.1 nM), nearly doubling evoked neurotrans-mitter release with no apparent effect on spontaneous3H-NE efflux. The response to 1 nM AII was abolished by the selective AII receptor antagonist saralasin([Sar1, Val5, Ala8]-angiotensin II; 500 nM), which alone did not modify3H-NE overflow. All-mediated effects on neurosecretion were partially additive to those of forskolin and were not potentiated by phosphodiesterase inhibition, suggesting that AII utilizes a mechanism other than increased cAMP synthesis to facilitate neurotransraitter release. AII also strongly enhanced calcium ionophore (A23187)-induced3H-NE release in iris-ciliary body segments, indicating that AII can modulate calcium-dependent exocytosis at step(s) distal to calcium influx. These results demonstrate that sympathetic nerves in the rabbit eye contain prejunctional, facilitatory AII receptors, and support the possible involvement of the renin-angiotensin system in regulation of ocular sympathetic neurotransmissionin vivo.