Background and objective:  Acid‐induced lung injury from aspiration is one of the most important causes of ARDS. Calcitonin gene‐related peptide (CGRP) is a neuropeptide that has various biological actions. The current study investigated whether CGRP might have pathophysiological roles in acid‐induced lung injury.Methods:  The investigations employed CGRP gene‐disrupted mice––mutant mice (CGRP–/–) and their littermate controls (CGRP+/+). Anaesthetized and mechanically ventilated mice received 2 mL/kg HCl (pH = 1.5) intratracheally. Lung wet‐to‐dry weight ratios were calculated to assess pulmonary oedema, total and differential cell counts of the BALF were determined, and measurements of myeloperoxidase activity were performed.Results:  Acid‐induced lung injury was characterized by an increase in lung permeability and respiratory failure. Disruption of the CGRP gene significantly attenuated acid‐induced injury, oedema and respiratory failure.Conclusions:  This study suggests that CGRP is involved in the pathogenesis of acute lung injury caused by acid aspiration and CGRP mutant mice may provide an appropriate model to study molecular mechanisms in this context.