Psychological stress can suppress baroreflex function, but the mechanism has not been fully elucidated. Nitric oxide in brain and adrenal cortex, as well as plasma glucocorticoids increase during stress and have been shown to suppress reflex gain in unstressed animals. Therefore, the purpose of this study was to test the hypothesis that stress, caused by exposure to a novel environment, decreases baroreflex gain in rabbits through the actions of nitric oxide to increase corticosterone release. Baroreflex control of heart rate and plasma corticosterone levels were quantified before and after blockade of nitric oxide synthase (NOS) with N -nitro-L-arginine (L-NNA, 20mg/kg, iv) in conscious rabbits exposed to a novel environment and the same rabbits once they had been conditioned to the environment. Stress significantly reduced baroreflex gain from -23.4 ± 2 to -12.2 ± 1.6 beats per min (bpm)/mmHg (p<0.05) and increased plasma corticosterone levels from 5.4 ± 0.7 to 15.5 ± 5.0 ng/ml (p<0.05). NOS blockade increased gain in stressed animals (to -27.2 ± 5.4 bpm/mmHg, p<0.05) but did not alter gain in unstressed rabbits (-26.8 ± 4.9 bpm/mmHg), such that gain was equalized between the two states. NOS blockade increased plasma corticosterone levels in unstressed animals (to 14.3 ± 2.1 ng/ml, p<0.05) but failed to significantly alter levels in stressed rabbits (14.0 ± 3.9 ng/ml). In conclusion, psychological stress may act via nitric oxide, independently of increases in corticosterone, to decrease baroreflex gain.