The presence of neural elements in synovial tissue proper has earlier been suggested on the basis of nonspecific silver impregnation techniques and is now confirmed in a study based on specific demonstration of cytoskeletal neurofilaments and various neuropeptides. With both the neurofilament and neuropeptide antisera, nerves were seen predominantly in a perivascular location, there being fewer nerves freely in the stromal tissue. In the synovium of patients with rheumatoid arthritis (RA), free stromal nerves stained with neurofilament antiserum often lacked neuropeptide immunoreactivity, while this was not the case in normal synovium or synovial samples from patients with osteoarthritis (OA). Furthermore, the intensity of staining of neurotransmitter peptides was weaker in RA than in OA or normal synovial tissue. It is suggested that neurogenic inflammation may play a role in RA and that neuropeptide nerves possibly release their mediators in RA.