Abstract This in vivo electrophysiological study concerns the role of nitric oxide (NO) in mechanical and thermal spinal nociceptive reflexes in α-chloralose anaesthetized rats. The effects of the NO synthase inhibitor, N G - nitro- l-arginine methyl ester ( l-NAME; 5–40 mg/kg i.v.) on reflexes were compared both in normal rats and in those with peripheral inflammation induced neurogenically (mustard oil) and non-neurogenically (carrageenan). Methoxamine (0.1 mg/kg i.v.) was used to mimic the marked hypertension caused by l-NAME. Thermal nociceptive reflexes were equally reduced by methoxamine and l-NAME in both normal and inflamed rats, implying that NO has no role in mediating thermal reflexes. However, l- (but not d-) NAME dose dependently and significantly inhibited mechanical reflexes in both carrageenan inflamed (to 37 ± 12% control) and mustard oil inflamed rats (to 75 ± 8% control). Moreover, these reductions were greater than those by methoxamine. In contrast, l-NAME did not reduce mechanical reflexes in rats with no inflammation or in spinalized rats with inflammation. The inhibition of mechanical reflexes with l-NAME in carrageenan inflamed rats was reversed and prevented by pre- or post-treatment with l- (but not d-) arginine (50–200 mg/kg i.v.). These data imply a supraspinal role for NO in mediating mechanical (but not thermal) nociceptive reflexes only in those rats with peripheral inflammation.