Prostaglandins (PGs) of the E series have been shown to modulate sympathetic neurotransmitter release in a variety of peripheral tissues and organs, including the eye. In this study, we evaluated the inhibitory effects of a series of naturally-occurring and synthetic PGs on field stimulation-evoked release of H-norepinephrine (H-NE) from isolated, superfused segments of human iris-ciliary body. Field-stimulated H-NE secretion was calcium-dependent, blocked by selective inhibitors of voltage-sensitive calcium and sodium channels, and originated from a desipramine-sensitive transmitter pool. Evoked H-NE release was inhibited in a concentration-dependent manner by PGE2(EC50=45 nM) and several closely related compounds with the following rank order of potency: sulprostone>16,16-dimethyl-PGE2>PGE2>11-deoxy-PGE1. By contrast, PGF2αwas relatively inactive (EC50>10μ, UM) in this system. None of the above compounds significantly modified spontaneous H-NE efflux. PGE2-mediated inhibition was not antagonized by the selective prostanoid EP -receptor antagonists AH 6809 (10μM) or SC-19220 (30μM), nor did these agents alone affect basal or field-stimulated3H-NE release. The results suggest that human ocular sympathetic nerves possess inhibitory PG receptors which have the pharmacological properties of the EP3subtype. These receptors may play a role in local feedback regulation of sympathetic transmission in the iris-ciliary body, and may contribute to symptoms of acute ocular inflammation, including vasodilation, miosis and hypotony.