The specific pathways through which radiation produces the lung injuries of pneumonitis (alveolitis) and fibrosis are unknown but may involve an altered immune response. In this study, we investigated the hypothesis that the radiation-induced lung phenotype of Ja18^–/– mice [which lack invariant natural killer T (iNKT) cells] is altered relative to that of C57BL/6J genetic background strain. After 18 Gy whole-thorax irradiation male C57BL/6J mice succumbed to respiratory distress at 28–30 weeks postirradiation and although confirmed by flow cytometric analysis to be deficient in iNKT cells, the postirradiation survival of Ja18^–/– mice was not significantly different from that of C57BL/6J mice (P = 0.87). Histologically, the lungs of both C57BL/6J and Ja18^–/– mice developed fibrosing alveolitis over a similar time course with the same severity (P = 0.15). Analysis of the bronchoalveolar lavage revealed that the C57BL/6J mice and female Ja18^–/– mice succumbed to respiratory distress with neutrophil numbers exceeding those of the Ja18^–/– male mice and untreated control mice. In conclusion, the radiation-induced lung disease of Ja18^–/– mice did not significantly differ from that of C57BL/6J mice.