It has been hypothetised that the nervous system contributes to the symmetrical response in rheumatoid arthritis. In order to elucidate this, the bilateral concentrations of substance P-like immunoreactivity (SP-LI), neurokinin A-LI (NKA-LI), calcitonin gene-related peptide-LI (CGRP-LI) and neuropeptide Y-LI (NPY-LI) in rat synovial fluid during acute monoarthritis were studied. Equal volumes (0.05 ml) of either Freund adjuvans, carrageenan 2%, substance P 10 −5 M or human recombinant interleukin-1α were injected into the right and saline into the left knee joint. Control rats were given saline bilaterally. Perfusates were obtained from both knees simultaneously at 2, 6 and 24 h after injection and were analysed by specific radioimmunoassays. Increase of SP-, NKA-, CGRP-and NPY-LI in synovial fluid occurred in both knees after injections with the pro-inflammatory substances into the right joints as compared to controls, except for unchanged SP-LI in the right knee joint after 24 h following hrIL-1α injection. There was, however, generally no significant difference in the peptide contents between the right knee (injected with pro-inflammatory substance) as compared to the left knee (given saline) at 2, 6 or 24 h after injection except at three occasions. The results show that experimentally induced monoarthritis induces bilateral changes in synovial fluid peptide content.