Cervical spinal cord injury results in interruption of sympathetic airway innervation, which originates from the upper thoracic spine, whereas parasympathetic nerve supply, arising in the vagal nuclei of the brainstem, remains intact. To assess the effect of such an altered neural environment on airway reactivity, bronchoprovocation testing was performed on eight subjects with nonacute traumatic lesions of the cervical spine, all of whom were lifetime nonsmokers without history of respiratory symptoms prior to their injury. Bronchial challenge was subsequently repeated after pretreatment with the anticholinergic agent, ipratropium bromide, an inhibitor of airway muscarinic receptors. All subjects demonstrated hyperresponsiveness to methacholine (the concentration of methacholine producing a fall in FEV1 of 20 percent from baseline [PC20] = 1.42 +/- 1.61 [SD] mg/ml). Airway hyperreactivity was completely blocked by pretreatment with inhaled ipratropium bromide (mean PC20 > 25 mg/ml [p < 0.0001]). The bronchial hyperresponsiveness observed in this population most likely reflects the loss of sympathetic airway innervation and resultant unopposed cholinergic bronchoconstrictor tone which results from transection of the cervical spine. Blockade of methacholine hyperresponsiveness with ipratropium bromide suggests a muscarinic receptor-mediated phenomenon.