Cannabinoids have an antinociceptive action in many pain models. We have investigated a possible modulatory role for Type 1 Cannabinoid receptors (CB(1)) on the release of excitatory transmitter Substance P from the adult mouse spinal cord after stimulation of nociceptor terminals by capsaicin. Capsaicin (0.1 - 10 microM) was applied to superfused cord sections and evoked a dose dependent release of SP above basal outflow of (23.36+/-2.96 fmol 8 ml(-1)). Maximum evoked SP release was obtained with 5 microM Capsaicin (262.4+/-20.8 fmol 8 ml(-1)). Higher capsaicin concentrations (50 - 100 microM) evoked less SP release. Superfusion of CB(1) antagonist SR141716A (5 microM) increased evoked SP release with capsaicin (0.1 - 10 microM) and reversed the reducing effect of high dose capsaicin (100 microM). Antagonism of CB(1) receptors in the spinal cord during capsaicin stimulation, is evidence of tonic CB(1) activity inhibiting the release of excitatory transmitters after activation of nociceptive neurones and is also indicative of endocannabinoid production during noxious stimulation.