The effects of nerve stimulation and topical administration of substance P (SP) on the blood flow supplying the rat knee joint were measured using laser Doppler perfusion imaging. A comparison was made between the responses found in normal knees and those observed in a group of animals with unilateral chronic inflammation induced by intra-articular injection of Freund's adjuvant, 1 week prior to experimentation. In control knees, nerve stimulation produced a frequency-dependent vasoconstriction over the range of 5-30 Hz and application of SP caused a dose-dependent vasodilatation. Chronically inflamed joints showed virtually no response to either nerve stimulation or SP application, suggesting a radical alteration in sympathetic and neuropeptidergic actions.