Abstract The involvement of nitric oxide (NO) in modulation of seizure susceptibility by δ-opioid agonist (+)-4-((alpha R)-alpha-((2 S, 5 R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl)- N, N-diethyl-benzamide (SNC80) was examined in mice. Systemic administration of SNC80 (0.1–5 mg/kg, intraperitoneally (i.p.)) decreased the threshold for clonic seizures induced by pentylenetetrazole. The non-specific NO synthase (NOS) inhibitor, N G-nitro- l-arginine methyl ester (3–20 mg/kg, i.p.), but not the specific inducible NOS inhibitor, aminoguanidine (50 and 100 mg/kg, i.p.) inhibited the proconvulsant effect of SNC80. On the other hand, NO substrate, l-arginine (30 and 60 mg/kg, i.p.) potentiated the proconvulsant effect of a lower dose of SNC80 (0.5 mg/kg). These results support the involvement of NO, produced by constitutive NOS, in the proconvulsant effect of the δ-opioid agonist.