Recent work has indicated that stem cells in adult bone marrow can give rise to cells of multiple lineages. Julia Dorin and co-authors are studying the potential of these cells to contribute to the upper respiratory tract, a property that could provide a new therapeutic approach for cystic fibrosis. On p. 2441, they report that bone-marrow-derived side population (SP) cells can contribute to the respiratory tract of mice in vivo. SP cells, which are isolated through their ability to exclude the DNA-binding dye Hoechst 33342, express markers consistent with a blood stem cell phenotype. The authors show that SP cells cannot contribute to embryos after blastocyst injection, to primary epithelial cultures grown at an air-liquid interface, or to denuded tracheal xenografts. However, they can contribute to the epithelial lining of the trachea in vivo following damage and repair. Thus, the authors conclude, SP cells can acquire the characteristics of airway epithelial cells, including cytokeratin expression, but only when exposed to in vivo cues.