<jats:title>Abstract</jats:title> <jats:p>The role of NKT cells in the pathogenesis of asthma and animal models of asthma is controversial. Although the initial mouse model study failed to identify an NKT cell requirement for induction of allergic airway inflammation or airway hyperresponsiveness (AHR), 2 subsequent mouse studies found both phenomena to be highly NKT cell-dependent. Some studies of human asthma patients also suggest strong involvement of NKT cells in airway inflammation, while others dispute this finding. To re-visit this issue at its origin, we evaluated the ability of ovalbumin (OVA) to induce allergic airway disease in BALB/c wild-type and NKT cell-deficient (CD1-deficient) mice, using a protocol in which mice were initially primed i.p. with OVA/alum, then inoculated intratracheally (i.t.) with OVA, as well as a protocol in which mice were inoculated i.t. with dust mite allergen without priming. Results from both studies demonstrated that wild-type and NKT cell-deficient mice develop similar airway eosinophilia, IL-4 and IL-13 responses, goblet cell hyperplasia and AHR (determined by both invasive and non-invasive methods). Flow cytometric analysis of lung and BAL lymphocytes from saline-, OVA-, and dust mite Ag-inoculated mice failed to demonstrate any specific staining for invariant NKT cells. We conclude that NKT cells are not required for allergen-immunized mice to develop full-blown allergic airway disease.</jats:p>