Cell-surface-associated glycoconjugates play important roles in cellular functions such as antigen presentation and cell adhesion, functions that may be modulated in patients with interstitial lung disease. Because carbohydrate residues can be recognized by specific lectins, we designed our study to establish baseline data for bronchoalveolar-lavage-derived cells from normal volunteers and to compare the lectin-binding properties of these cells with cells recovered from patients presenting with interstitial lung disease. Cells were obtained from patients with idiopathic pulmonary fibrosis (n = 10), patients with sarcoidosis (n = 20), and patients receiving amiodarone without evidence of clinical lung disease (n = 10) as well as from normal volunteers (n = 8). To determine the pattern of cell-surface glycoconjugate expression on alveolar macrophages (AM), we used a panel of 21 fluorochrome-coupled plant lectins and employed flow cytometry to determine their binding to AM. The labeling profiles of AM were found to be highly reproducible for normal subjects. At the lectin concentrations used for this study, some lectins showed very little binding to AM and some displayed intermediate binding, but the majority of the lectins labeled nearly all AM in samples. Fluorescence intensity varied characteristically for cells labeled with different lectins, providing further refinement and permitting discrimination beyond that provided by data restricted to percent of labeling. AM from patients with interstitial lung disease showed increased binding for the plant-derived lectins PNA, UEA-I, BSL-I, VVL, and SJA compared with AM from normal subjects, being most augmented for AM from patients with idiopathic pulmonary fibrosis. Because peripheral blood monocytes from normal subjects show a higher percentage of labeling with PNA, UEA-I, SJA, and BSL-I than did AM, the increased expression of binding sites for these four lectins by AM from patients with interstitial lung disease may reflect the influx of immature blood monocytes and/or the emergence of a proinflammatory macrophage phenotype. This study demonstrated heterogeneous expression of surface carbohydrate residues by AM and blood monocytes from normal subjects and alterations in carbohydrate receptor expression in interstitial lung disease. Lectin-binding properties may prove useful, therefore, in the evaluation of mononuclear phagocyte populations in interstitial lung disease, especially by the identification of functional subsets and/or changed activation states.