Rationale: Although corticosteroids are highly effective at preventing allergen-induced increases in goblet cell numbers, in unpublished experiments, we have observed a rebound increase in goblet cell numbers in mice, following the simultaneous withdrawal of corticosteroid and cessation of exposure to allergen, that reached levels greater than those observed in mice exposed to allergen alone without any corticosteroid treatment. Objectives: Formally explore the goblet cell hyperplasia rebound observed following corticosteroid withdrawal in allergen exposed mice and determine the mechanism responsible for this previously undescribed pathology. Methods: Mice airways were assessed for mucin containing goblet cells following exposure to varying durations of allergen and corticosteroid. Measurements and Main Results: We confirmed that the simultaneous withdrawal of corticosteroid and cessation of exposure to allergen resulted in a goblet cell hyperplasia rebound that reached levels greater than those observed in allergen exposed corticosteroid naive mice. Importantly, the goblet cell rebound was associated with a significant airway dysfunction, that was greater than that observed in allergen exposed corticosteroid naive mice. The goblet cell hyperplasia rebound is independent of the type of corticosteroid or allergen and was associated with an increased level of bronchoalveolar lavage interleukin-13. Inhibition of interleukin-13, but not CD4⁺ T cells, completely inhibited the goblet cell hyperplasia rebound and critically the associated airway dysfunction. Conclusions: These findings suggest that certain corticosteroid treatment regimes may actually potentiate airway remodeling and dysfunction in patients with asthma and lead to increased exacerbations and worsening of asthma symptoms.