Fanconi anemia is a genetic disorder characterized by hypersensitivity to DNA interstrand cross-linking agents and a defect in the ability to repair this type of damage. This deficiency correlates with reduced levels of αII spectrin, a structural protein involved in the repair of DNA interstrand cross-links. The present study addresses the question of whether the reduced levels of αII spectrin in FA-A, FA-C, and FA-G cells are due to reduced expression of this protein and/or due to differences in the three regions of alternate splicing of αII spectrin mRNA. Relative quantitative RT-PCR showed that levels of αII spectrin mRNA in the three FA cell lines were similar to normal as were the sites of alternative mRNA splicing. These results indicate that decreased levels of αII spectrin in these FA cell lines are not due to reduced expression of αII spectrin mRNA or due to differences in regions of alternate splicing of these transcripts, but rather appear to be related to reduced stability of αII spectrin in these cell lines.