We demonstrate the presence of nitric oxide synthase containing fibers within the guinea pig trigeminal motor nucleus and describe the effects of nitric oxide (NO) on trigeminal motoneurons. Using immunohistochemical techniques, we observed nitrergic fibers displaying varicosities and giving rise to bouton-like structures in apposition to retrogradely labeled motoneuron processes, most of which were dendrites. NO-donors evoked a membrane depolarization (mean 7.5 mV) and a decrease in rheobase (mean 38%). These substances also evoked an apparent increase in an hyperpolarization-activated cationic current (I(H)). These changes were not accompanied by any modification of the motoneurons' input resistance or time constant. The effects were suppressed by blocking the cytosolic guanlyate cyclase. A membrane-permeant cyclic guanosine 3,5'-monophosphate (cGMP) analogue mimicked the effects of NO. There was a considerable increase in synaptic activity following NO-donors or db-cGMP application. Tetrodotoxin supressed the increase in synaptic activity evoked by NO-donors. The histological and electrophysiological evidence, taken together, indicates the existence of a nitrergic system able to modulate trigeminal motoneurons under yet unknown physiological conditions.