Interactions of macrophages with epithelium represent one of the pathways involved in regulating local immune mechanisms. We studied the effect of cell-cell contact with an epithelial monolayer on the phenotype of macrophages. Human monocytes and THP-1 macrophages were co-cultured with monolayers of human bronchial epithelial cells (HBECs), the alveolar type II-like cell line A549, renal adenocarcinoma epithelial cells (RA), and the lung fibroblast strain HFL-1. The expression of CD11b, CD14, CD54, and HLA-DR was measured by immunocytochemistry and flow cytometry and showed epithelial cell induction of CD54 and HLA-DR in monocytes and of all antigens in THP-1 cells. Co-culture with fibroblasts did not change the phenotype of macrophages. Separation by a filter insert inhibited most of the effects. Culture supernatants did not induce prominent phenotypic changes. Cell-cell contacts with epithelium appear to be of importance in regulating the phenotype of macrophages.