Capsaicin is the pungent component of chilli peppers that concomitantly activates and desensitizes C-fibre and Adelta sensory nerve fibres. Stimulation causes an acute neurogenic response including vasodilation, plasma extravasation and hypersensitivity. However, in the present study we have shown that capsaicin produces a dose-dependent vasoconstrictor effect in the mouse knee joint via Transient Receptor Potential Vanilloid 1 (TRPV1) receptor activation. A (125)I-albumin accumulation technique showed that the intravascular volume of capsaicin-treated joints in wild type (WT) mice was significantly reduced compared to TRPV1 knockout mice (p<0.01). Similarly, a laser Doppler technique showed significantly reduced blood flow in the capsaicin-treated joints of WT compared to TRPV1 knockout mice (p<0.001). Pretreatment with guanethinidine (50 mg kg(-1), i.p.) had no effect on the vasoconstriction. These data are important considering the involvement of TRPV1 receptors in joint disease. The mechanisms underlying the vasoconstriction therefore require further investigation.