In situ hybridization using cDNAs complementary to specific regions of the mRNAs encoding four members of the FOS transcription factor gene family reveals modest levels of hybridization over superficial lamina of the nucleus caudalis of the spinal tract of the trigeminal in sections taken from unstimulated brains. Fos B expression is markedly and rapidly enhanced ipsilateral to electrical stimulation of the trigeminal ganglia. c-fos mRNA also changes; these differences contrast with the lack of significant changes in the low basal levels of expression of fra-1 and fra-2 mRNAs. The prominent change in fos B mRNA is mediated largely by an increase in the number of neurons that express hybridization densities above background after stimulation. This result, taken together with data on stimulation-induced changes in expression of preproenkephalin and other AP-1 transcription factors in wild-type animals and stimulation-induced changes in CAT activity in transgenic mice expressing portions of the proenkephalin promoter, is consistent with a role for the enhanced fos B expression in upregulation of expression of preproenkephalin in these neurons.