Calcitonin gene-related peptide (CGRP) released from vasodilator nerves is implicated in the gastroprotective action of capsaicin. This experimental paradigm was used to prove the effectiveness of a monoclonal anti-CGRP antibody. The experiments were performed in anaesthetized rats in which intragastric capsaicin (0.5 mg/kg) reduced gastric injury due to ethanol (50%) by 72%. The protective effect of capsaicin was abolished by close arterial administration of the anti-CGRP antibody #4901 (5 mg) to the stomach. A monoclonal antibody to keyhole limpet haemocyanin was without effect. These data establish anti-CGRP antibody #4901 as a tool to neutralize endogenously released CGRP and show that CGRP is indispensable for the gastroprotective action of capsaicin.