Since shedding of columnar, but not basal, epithelial cells is common in asthma, cell adhesion molecules such as CD44, which are differentially expressed on these cell types, are likely to be important in this disease. In bronchial epithelium of asthmatic and nonasthmatic subjects, CD44 isoforms have been localized by light- and electron-microscopic immunocytochemistry. Immunoreactivity for total CD44 (mAb Hermes-3/mAb 25.32) and for isoforms containing CD44v9 (mAb 11.24), CD44v6 (mAb 11.9), and CD44v4 (mAb 11.10) have been compared. In nonasthmatic samples, CD44s and CD44v9 were seen on basal but not columnar epithelial cells. Weak CD44v6 immunoreactivity was found infrequently in the bronchus, whereas CD44v4 immunoreactivity was absent. This indicates the presence of a distinct population of basal cells that express CD44. No CD44 was detected in areas of close cell-cell or cell-matrix contact, thus precluding the involvement of CD44 in stable adhesion in these areas. CD44 immunoreactivity was locally increased in areas showing morphologic damage to the epithelium. In epithelium from asthmatic subjects, the mean level of CD44 immunoreactivity on basal-cell membranes was doubled (4.3 versus 2.0 gold particles/microns membrane) as compared with nonasthmatic subjects. Increased expression of CD44 in asthmatic subjects, suggests that it has a significant role in the pathobiology of this disease, whereas the restricted distribution of this increase supports an association with repair rather than with inflammatory processes.