Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activity and the central terminal fields of branches of the mandibular and chorda tympani nerves were visualized histochemically at the same time using transganglionic transport of wheat germ agglutinin conjugated with horseradish peroxidase. The blue NADPH-d-positive neurons comprised a sparse network in the dorsomedial spinal trigeminal subnucleus oralis and a dense one in the rostral lateral division of the nucleus of the solitary tract. In the subnucleus caudalis, most labeled neurons were in the superficial zone, and smaller numbers were in the magnocellular zone. The NADPH-d-positive neurons in the subnucleus oralis and the nucleus of the solitary tract overlapped mostly with the transganglionically labeled terminal field from the lingual nerve, partly with the terminal field from the inferior alveolar and chorda tympani nerves, and rarely with the terminal field from the mental nerve. The NADPH-d-positive neurons in the dorsomedial paratrigeminal nucleus and subnucleus caudalis overlapped mostly with the terminal field from the lingual nerve, partly with the terminal field from the inferior alveolar and mental nerves and never with the terminal field from the chorda tympani. A statistically significant reduction in the number of NADPH-d-positive neurons was seen bilaterally in subnucleus oralis and the nucleus of the solitary tract when the lingual nerve was transected. Inflammatory insults to the lingual nerve or tooth pulps significantly increased the number of NADPH-d-positive neurons in subnucleus oralis, the nucleus of the solitary tract, and subnucleus caudalis. These results show that the NO/cyclic GMP system in the trigeminal and solitary nuclei is differentially regulated trans-synaptically by trigeminal afferents depending on the nucleus and sensory modality. (C) 1998 Elsevier Science B.V.