By using in situ hybridization histochemistry and immunohistochemistry, neuropeptide Y (NPY) and NPY (Y1) receptor mRNA as well as NPY-like immunoreactivity were examined in the lumbar spinal cord (L4-L5) and in dorsal root ganglia (DRG, L5) in rats injected with complete Freund's adjuvant (CFA) into the hindpaw. A rapid and marked increase in NPY mRNA expression was observed in ipsilateral dorsal horn neurons 6 hr after inoculation as compared to the contralateral side. This was mainly found in the medial part of spinal lamina II. The peak level (88% increase) was reached at 3 d. In adjacent sections of the spinal cord, 96% and 33% increases were found in the number of dynorphin and enkephalin mRNA-positive neurons, respectively. Unilateral inflammation also induced a moderate increase in NPY-like immunoreactivity and the number of NPY-immunoreactive neurons in the medial part of the ipsilateral spinal dorsal horn. In addition, a marked elevation in the expression of c-Fos-like protein was observed in ipsilateral spinal neurons in laminae I, II, and V. However, no NPY mRNA-positive or NPY- immunoreactive neurons were found in the ipsilateral and contralateral DRGs in rats receiving CFA injection. Furthermore, a marked upregulation of NPY (Y1) receptor mRNA expression was detected in the ipsilateral spinal dorsal horn 1 d and 3 d after inoculation. These Y1 receptor mRNA-positive cells were mainly distributed in the medial laminae II and III. Numerous Y1 mRNA-positive, small neuron profiles were found bilaterally in the DRGs in CFA-treated rats. CFA evoked a 34% increase in the number of Y1 mRNA-positive neurons in ipsilateral DRGs as compared to contralateral DRGs. The distinct upregulation of NPY and NPY (Y1) receptor in response to peripheral inflammation suggests an involvement of NPY in the response to inflammation and in nociception.