Remodeling of the airway wall occurs in adults with asthma, and reticular basement membrane (RBM) thickening is pathognomonic of the asthma process. To investigate whether RBM thickening is present in children with difficult asthma and comparable to that seen in adults with asthma, we used light microscopy to measure RBM thickness in plastic-embedded endobronchial biopsy sections from 19 children with difficult asthma who were prescribed 1,600 microg/day or more of inhaled steroids (age range, 6-16 years), 10 children without asthma (7-16 years), and three adult groups: 8 healthy control subjects (21-42 years), 10 mild steroid-naive subjects with asthma (18-41 years), and 6 adults (3 steroid naive and 3 on inhaled steroids) intubated after a life-threatening attack of asthma (20-64 years). RBM thickness in the children with asthma was similar to that in adults with either mild or life-threatening asthma (median 8.2 [range 5.4-11.1] versus 8.1 [5.8-10.0] and 7.2 [2.8-10.0] microm, respectively) and greater than either adult or pediatric control subjects (8.2 [5.4-11.1] versus 4.4 [3.2-6.3] microm, p < 0.01, and 4.9 [3.7-8.3] microm, p < 0.01). We conclude that RBM thickening is already present in children with difficult asthma and to a similar extent to that seen in adults with asthma. In addition, we find no association with age, symptom duration, lung function, or concurrent eosinophilic airway inflammation.