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An access to the medullary brain stem allowed extracellular action potentials to be recorded from neurons in the spinal trigeminal nucleus that received afferent input from the exposed dura. Slow intravenous infusion of the NO donor, sodium nitroprusside (SNP, 50 \u03bcg\/kg), transiently increased spontaneous activity in a subset of neurons and, with a latency of 50 min, caused a progressive increase in impulse activity across the entire sample of neurons. A similar pattern of delayed activation was seen after topical application of the same dose of SNP onto the exposed medulla. Slow injection of the nonspecific inhibitor of NO synthase, N<jats:sup>\u03c9<\/jats:sup>-nitro-l-arginine methyl ester (20 mg\/kg), reduced the spontaneous activity in all neurons within 15 min. The results suggest that NO can induce delayed, slowly developing activation of central trigeminal neurons and that endogenous release of NO may contribute to the ongoing activity of these neurons. The delayed changes in neuronal activity may include gene expression of pro-nociceptive mediators. 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