1 The effect of the nitric oxide synthase (NOS) inhibitor, 7-nitro indazole (7-NI), on sympathetic and purinergic neurotransmission in the rat isolated vas deferens preparation has been studied.2 7-NI (50-200 JLM) caused a dose-and frequency-dependent inhibition of the phasic (predominantly purinergic) contractile response of the rat vas deferens to electrical (field) stimulation (100 V, 0.5 ms). Greatest inhibition occurred at lower frequencies of stimulation (0.1-1O Hz). The sustained tonic contractile response (predominantly noradrenergic) was inhibited only at a high frequency of stimulation (60 Hz) and only at the highest concentration of 7-NI studied (200 J.M). indicating the absence of involvement of a2-or ,-adrenoceptors in this response.5 7-NI (50-600 LM) caused dose-related inhibition of contractions elicited by addition of a depolarizing concentration of KCI (64 mM). 6 The effect of 7-NI (100IM) on the phasic contractile response to field stimulation (0.1 and 2.0 Hz) was unaffected by preincubation of preparations with L-arginine (1 mM). Neither L-arginine (1 mM) nor NC nitro L-arginine methyl ester (L-NAME, 100 LM) affected the response of the vas deferens to field stimulation at 0.1 or 2.0 Hz. Nitric oxide synthase (NOS) enzyme activity, measured as the conversion of [3H]-L-arginine to [3H]-citrulline, was not detectable in rat vas deferens homogenates. 7 7-Nr preferentially inhibits the purinergic component of the response of the rat vas deferens to field stimulation. The mechanism of action of 7-NI is not known but is not related to NOS inhibition. It seems likely that 7-NI combines an antagonist action at smooth muscle cell P2X-purinoceptors with the ability to inhibit the cellular influx of calcium ions. Although these hitherto unrecorded effects of 7-NI occur at relatively high concentrations, the effects described may contribute to the pharmacological effects of this NOS inhibitor.