The occurrence of substance P (SP) and calcitonin gene-related peptide (CGRP) was assessed in the ankle joints and dorsal root ganglia (L2-L6) by immunohistochemistry and radioimmunoassay (RIA) after unilateral sciatic nerve section in adjuvant arthritis. Nerve section in arthritic rats had no clear-cut effect on warmth, redness, and swelling of ankle joints, but significantly affected the occurrence of SP and CGRP. Immunohistochemical analysis showed an almost complete disappearance of SP-positive fibers in the ipsilateral ankle joint in normal rats after axotomy, whereas in arthritic rats occasional SP-positive fibers remained. In dorsal root ganglia, only occasional SP-positive cells could be detected in normal and arthritic rats after axotomy. A similar but somewhat less pronounced effect of axotomy was noted for neuronal CGRP-LI. RIA showed a decrease in SP in ankle joints by 45% in normal rats and 58% in arthritic rats; the decrease in CGRP was 41% and 47%, respectively. In dorsal root ganglia, the decrease in SP after surgical denervation was 25% in normal rats and 54% in arthritic rats; the decrease in CGRP was 18% and 27%, respectively. The tissue concentrations of SP and CGRP in ipsilateral ankle joints and dorsal root ganglia were consistently correlated in normal as well as arthritic rats. The present study shows that an interruption of the nerve supply to joints cannot fully prevent the development of arthritis, although it significantly reduces the occurrence of sensory neuropeptides.