1. N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO biosynthesis, which blocks basal NO production, caused a similar increase of mean arterial pressure (MAP) in control hyper- and hypothyroid rats at the lowest dose, however, smaller pressor effects were observed with increasing doses in hyper- and hypothyroid rats. An additional dose of L-NAME (30 mg/kg), which produced no further increase in pressure, killed 90% of the hyperthyroid rats, whereas hypothyroid and control rats survived this additional dose. 2. The systemic responses to acetylcholine (ACh), an endothelium-dependent vasodilator that stimulates NO production/release, were significantly increased in hypothyroid rats, while hyperthyroid rats showed no significant differences when compared with controls. However, 10(-8) M ACh killed hyperthyroid rats, whereas control and hypothyroid rats survived this dose. 3. The maximal hypotensive response to sodium nitroprusside (SNP), an agonist that generates NO, was similar in intact controls, hyper- and hypothyroid rats. 4. These data indicate that hyper- and hypothyroidism show a reduction in basal NO synthesis/release, this reduced systemic NO tone being essential for life in hyperthyroid rats; whereas the response to ACh is not reduced and the hypotensive response to SNP did not differ between groups, indicating that the responsiveness of the systemic circulation to NO is not altered in either thyroid disorder.