Using immunohistochemistry and in situ hybridization, the expression of galanin (GAL)/galanin message associated peptide (GMAP)-, neuropeptide Y (NPY)-, vasoactive intestinal polypeptide (VIP)/peptide histidine isoleucine (PHI)- and nitric oxide synthase (NOS)-like immunoreactivities and mRNAs, and NPY receptor mRNA was studied in normal trigeminal and nodose ganglia and 14 and 42 days after peripheral axotomy. In normal trigeminal ganglia about 11% of the counted neuron profiles contained GAL mRNA, 4% NOS mRNA, 5% NPY mRNA, 7% VIP mRNA, and 19% NPY receptor mRNA. Peptide mRNA- and NPY receptor mRNA-positive neuron profiles were small in size. Fourteen days after axotomy a marked increase in the number of GAL mRNA-(34% of counted neuron profiles), NPY mRNA-(54%) and VIP mRNA-(31%) positive neuron profiles, and a moderate increase in the number of NOS mRNA-(22%) positive neuron profiles were observed in the ipsilateral trigeminal ganglia. The GAL/GMAP, VIP- and NOS-positive profiles were mainly small, the NPY-positive ones mostly large. NPY receptor mRNA was expressed in some large neurons. In normal nodose ganglia, about 3% of the counted neuron profiles contained GAL mRNA, 3% NPY mRNA, 17% NOS mRNA and less than 1% VIP mRNA. Fourteen days after peripheral axotomy, a marked increase in the number of GAL mRNA-(78% of counted neuron profiles), NOS mRNA-(37%) and VIP-(46%) mRNA-positive neuron profiles was seen in the ipsilateral nodose ganglia. The number of NPY-positive (23%) neurons was moderately increased, mainly in small neuron profiles. There were no NPY receptor mRNA-positive neurons, either in normal nodose ganglia or in nodose ganglia ipsilateral to the axotomy. In contralateral nodose ganglia the number of GAL- and NPY-positive neuron profiles was slightly increased, and VIP cells showed a moderate increase. Immunohistochemical analysis revealed parallel changes in expression of peptides and NOS in both trigeminal and nodose ganglia, demonstrating that the changes in mRNA levels are translated into protein. Finally, although not quantified, similar upregulations of peptide and NOS mRNA levels were observed in both ganglia 42 days after nerve injury provided that regeneration was not allowed, suggesting that the changes are long lasting. The present results show that the effect of axotomy on peptide and NOS expression in the trigeminal and nodose ganglia is similar to that previously shown for lumbar dorsal root ganglia. However, no mRNA for the NPY Y1 receptor could be detected in the vagal system. In general the mechanism(s) for and the purpose(s) of the messenger regulation in response to axotomy may be similar in these different sensory systems (dorsal root, trigeminal and nodose ganglia).