The role of prostaglandins in mediating angiotensin effects on autonomic neurotransmission was assessed. This was accomplished by examining the angiostensin-induced production of prostaglandins (PGE) and suppression of non-adrenergic (purinergic) neurotransmission in the presence and absence of cyclo-oxygenase inhibitors. The vas deferens of the rabbit was utilized for these studies because this preparation has a predominant non-adrenergic neurogenic component. Both angiotensins II and III enhanced PGE production and reduced non-adrenergic neurogenic contractions in a concentration-dependent manner from 1 to 1000 mM. Furthermore, indomethacin (2.8 μM) and eicosatetraynoic acid (10 μM) eliminated the inhibitory effect of the angiotensins on non-adrenergic neurotransmission. However, acetylsalicylic acid (10 μM) prevented the production of PGE in response to the angiotensins but failed to alter the suppression of non-adrenergic neurotransmission. The latter data are inconsistent with the hypothesis that PG's mediate angiotensin-induced depression of non-adrenergic neurotransmission. The mechanism by which indomethacin and eicosatetraynoic acid prevent angiotensin effects on non-adrenergic neurotransmission was not elucidated but previous reports suggest that these agents may act as angiotensin receptor antagonists. All of the cyclo-oxygenase inhibitors examined tended to potentiate angiotensin effects on adrenergic neurotransmission.