The effects of the endogenous cannabinoid anandamide were studied on peripheral, polymodal nociceptors recorded from normal and chronically inflamed (Freund's adjuvant) knee joint afferents in rats anaesthetized with pentobarbitone. Anandamide (860 nmol) caused a rapid, short lasting excitation of a sub-population of capsaicin-sensitive nociceptive afferents in normal knee joints (7.2+/-2.3 impulses s(-1); n=15 units from five animals). In arthritic joints there were 9.7+/-3.0 impulses s(-1) (n=11 from six animals), which was not significantly different from normal joints. The excitation was dose dependent (8.6 - 2900 nmol) and mediated by activation of the vanilloid receptor (VR(1)) as it was abolished by the VR1 antagonist capsazepine (1 mg kg(-1)). Our results show that anandamide, at high doses, can activate nociceptive afferents innervating the rat knee joints, in contrast with its widely described analgesic actions.