This is a study of neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)- like immunoreactivity(-LI) in the cerebrospinal fluid (CSF), plasma and perfusates (PF) from the temporomandibular joints (TMJs) of the rat during acute inflammation. Substance P (10(-5) M, 0.01 ml) was injected into the right TMJ of the rat. The TMJs of the control rats, were injected with 0.01 ml saline. CSF, plasma and PF from TMJs were taken at 2, 6 and 24 hrs following injection. The neuropeptide-LI level was analysed by specific radioimmunoassays and compared with control values. Unilateral injection of SP into the rat TMJ resulted in a general increase in the concentration of NKA-, CGRP- and NPY-LI in the TMJ PF at 2, 6 and 24 hrs following injection. In the CSF NKA- and CGRP-LI was increased leaving the NPY-LI unaffected. In general no changes in peptide concentrations were seen in plasma. The results indicate that SP directly or indirectly induces a local release of peptides through an action at sensory and sympathetic neurons.