Both insulin, depending on the glycemic state, and nitric oxide (NO), depending on the experimental conditions, have been suggested to have either proconvulsant or anticonvulsant effects. It is also known that NO plays an important role in some of the peripheral effects of insulin. The aim of the present study was to investigate the effects of NO and insulin against convulsions produced by pentylenetetrazole (PTZ, 60 mg/kg, i.p.) in mice and whether NO plays a role in the effect of insulin. Nitric oxide synthase (NOS) inhibitor, N-G-nitro-L-arginine-methyl ester (L-NAME, 1-100 mg/kg, i.p.) shortened the onset of PTZ-induced convulsions and increased the incidence and mortality rate, at the higher doses. Insulin (1 U/kg, i.p.), when given with dextrose (3 g/kg, i.p.) to counteract the hypoglycemic effect of the hormone, prolonged the onset of convulsions and decreased the incidence and mortality rate. L-NAME pretreatment (3 mg/kg, i.p.), at the dose which it produced no effect on PTZ-induced convulsions, attenuated the protective effect of 1 U/kg insulin + 3 g/kg dextrose combination significantly. Concomitant administration of the NO synthesis precursor, L-arginine (500 mg/kg), completely reversed this facilitatory effect of L-NAME. Our results indicate that NO has a protective effect against PTZ-induced convulsions in mice; insulin has a similar effect when given with dextrose; and, NO production may play an important role in the anticonvulsant effect of insulin.