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A modification of the intravenous regional anaesthesia technique was used to assess the peripheral antinociceptive effect of remoxipride, clonidine and fentanyl. Drugs administered intravenously via peripheral catheters were restricted to the distal limb and nociceptive threshold test site by prior inflation of a tourniquet proximal to both the catheter and a threshold-testing device. Lignocaine (1 mg/kg) induced peripheral antinociception during tourniquet inflation. Clonidine (6 micrograms/kg) only induced significant elevations in thresholds after tourniquet deflation. A low dose of remoxipride (2 mg/kg), which had no systemic antinociceptive effect, produced antinociception after its restriction to the periphery. Peripheral administration of saline and tourniquet-induced restriction of blood flow to the distal limb did not alter threshold values. Peripheral administration of fentanyl was used to test a further modification of the injection protocol designed to reduce the incidence of leakage into the systemic circulation. Fentanyl administration (11.2 micrograms/kg) failed to elicit an increase in thresholds when it was restricted to the distal limb test site. The contribution of a peripheral mechanism to the antinociception induced by systemic administration of a higher remoxipride dose (7.5 mg/kg) was investigated using an inflated tourniquet to exclude remoxipride from the periphery. Exclusion of remoxipride from the periphery reduced its antinociceptive effect, i.e. threshold values were lower than if remoxipride was allowed free access to the limb prior to tourniquet inflation. The technique described here was effective in demonstrating that the increase in noninflammatory nociceptive thresholds seen with clonidine and fentanyl is not peripherally mediated whilst that seen with remoxipride has a peripheral component.