Synovial capsule in cats is extensively innervated by a network with axonal diameter ranging from 0.6-3 microns according to its position and neuropeptide content. Nerve markers such as Neuron Specific Enolase (NSE) and Neurofilament triplet protein (NF) could be observed only when the axonal fibre attained a critical diameter of over the 3 microns limit. The relatively thick fibres (1-3 microns) show positive immunoreactivity for Substance P (SP), 5-hydroxytryptamine (5-HT), and Vasoactive Intestinal Peptide (VIP), and seldom coreact with NSE and NF, whereas, the thinnest fibres (0.6-0.8 microns) characterized to contain either Methionine or Leucine Enkephalin (M-Enk, L-Enk) did not coreact positively with axonal markers. We found that different anesthetics may effect variably the immunoreactivity of some neuropeptides (SP, L-Enk, 5-HT) while others (VIP, M-Enk) remained unaffected. Based on our data and the few reported ones in the pertinent literature, it is judged that urethane is the anesthetic of choice in experimental studies of neuropeptides. Our findings of isolated positive immunoreactive cell bodies to enkephalin in synovia might suggest the presence of intrinsic relay system, where the enkephalin acts as suppressor of SP and VIP release from the sunovium nerve terminals. Such a local inter-relationship between different neuropeptide systems might have a practical role on the understanding of the pathogenesis of different arthritic processes as well as therapeutic strategy in the future.