The purpose of these studies was to determine the effects of L-arginine-derived nitric oxide (NO) synthesis on neuronal activity in solitary tract nucleus (NTS) neurons. Single unit activity was recorded extracellularly from medial NTS neurons in Fischer-344 rats in vivo and in vitro. In anesthetized rats with arterial pressure maintained constant, NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv), an inhibitor of NO synthesis, decreased the discharge rate in 12 of 14 neurons and increased the discharge rate in two. After injection of L-NAME, the slowing of neuronal activity began within 2-5 min, and maximal responses were observed 12-15 min after injection. The decreases in activity were reversed within 12-15 min with L-arginine (30 mg/kg iv) or immediately with nitroglycerin (NTG, 10-30 micrograms/kg iv). In superfused rat brain slices, the discharge rate was reduced by 1 mM L-NAME in seven neurons, increased in two, and unchanged in one. The decreases in discharge rate were reversed by 2 mM L-arginine (4 of 6 neurons) and by 10-30 microM NTG (6 of 7 neurons). The results show that L-arginine-derived NO can affect the spontaneous discharge rate of NTS neurons. We conclude that NO may influence the excitability of NTS neurons involved in central autonomic control.